<SEC-DOCUMENT>0000874015-22-000168.txt : 20221109
<SEC-HEADER>0000874015-22-000168.hdr.sgml : 20221109
<ACCEPTANCE-DATETIME>20221109143831
ACCESSION NUMBER:		0000874015-22-000168
CONFORMED SUBMISSION TYPE:	10-Q
PUBLIC DOCUMENT COUNT:		61
CONFORMED PERIOD OF REPORT:	20220930
FILED AS OF DATE:		20221109
DATE AS OF CHANGE:		20221109

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			IONIS PHARMACEUTICALS INC
		CENTRAL INDEX KEY:			0000874015
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		IRS NUMBER:				330336973
		STATE OF INCORPORATION:			CA
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		10-Q
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		221372076

	BUSINESS ADDRESS:	
		STREET 1:		2855 GAZELLE COURT
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92010
		BUSINESS PHONE:		7609319200

	MAIL ADDRESS:	
		STREET 1:		2855 GAZELLE COURT
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92010

	FORMER COMPANY:	
		FORMER CONFORMED NAME:	ISIS PHARMACEUTICALS INC
		DATE OF NAME CHANGE:	19930328
</SEC-HEADER>
<DOCUMENT>
<TYPE>10-Q
<SEQUENCE>1
<FILENAME>form10q.htm
<DESCRIPTION>IONIS PHARMACEUTICALS INC 10-Q 9-30-2022
<TEXT>
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<div>UNITED STATES</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 18pt; font-weight: bold;"><!--PROfilePageNumberReset%Num%1%%%-->SECURITIES AND EXCHANGE COMMISSION</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Washington, DC 20549</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Mark One)</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Exact name of Registrant as specified in its charter)</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Securities registered pursuant to Section 12(b) of the Act:</div>
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<div style="text-align: left; text-indent: 18pt;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of &#8220;large accelerated filer,&#8221; &#8220;accelerated filer,&#8221; &#8220;smaller reporting company,&#8221; and &#8220;emerging growth company&#8221; in Rule 12b-2 of the Exchange Act.</div>
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    <td style="width: 50%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Emerging Growth Company <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonNumeric name="dei:EntityEmergingGrowthCompany" id="Fact_b324ad6856c946fcb60ff103712caa84" contextRef="c20220101to20220930" format="ixt-sec:boolballotbox">&#x2610;</ix:nonNumeric></span></div></td>
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<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#x2610;</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant is a shell company (as defined in Rule 12(b)-2 of the Securities Exchange Act of 1934). Yes <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonNumeric name="dei:EntityShellCompany" id="Fact_3bc115f63d5d44be8cdbc2eba0d2aab7" contextRef="c20220101to20220930" format="ixt-sec:boolballotbox">&#x2610;</ix:nonNumeric></span> No <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#x2612;</span></div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The number of shares of voting common stock outstanding as of November 3, 2022 was <ix:nonFraction name="dei:EntityCommonStockSharesOutstanding" id="Fact_3a99a0f5d2b046e59520e673d7e403f7" contextRef="c20221103" unitRef="U001" decimals="INF" scale="0" format="ixt:num-dot-decimal">142,050,336</ix:nonFraction>.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Index"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FORM 10-Q</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">INDEX</div>
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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART I</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FINANCIAL INFORMATION</div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 1:</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financial Statements:</div></td>
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    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#BalanceSheet" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Balance Sheets</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> as of </span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited) and </span>December 31, 2021</div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
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    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#IncomeStatementQ2Q3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Operations</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the three and </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ComprehensiveLossQ2Q3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Comprehensive Loss</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the three and </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#EquityQ1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Stockholders&#8217; Equity</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the three and </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#CashFlows" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Cash Flows</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Notes" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Notes to Condensed Consolidated Financial Statements (unaudited)</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 2:</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item2MDAQ2Q3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations:</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#OverviewQ2Q3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Overview</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">29</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ResultsOfOperationsQ2Q3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Results of Operations</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#LiquidityQ2Q3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liquidity and Capital Resources</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 3:</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item3MarketRisk" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Quantitative and Qualitative Disclosures about Market Risk</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 4:</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item4Controls" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Controls and Procedures</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART II</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#PARTII" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">OTHER INFORMATION</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41</div></td>
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    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 1:</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ITEM1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Legal Proceedings</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 1A:</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ITEM1A" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk Factors</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 2:</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ITEM2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unregistered Sales of Equity Securities and Use of Proceeds</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60</div></td>
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    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 3:</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ITEM3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Default upon Senior Securities</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60</div></td>
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  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 4:</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ITEM4" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mine Safety Disclosures</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60</div></td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 5:</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ITEM5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other Information</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60</div></td>
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  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 6:</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ITEM6" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exhibits</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61</div></td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td colspan="2" style="width: 92.08%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#SIGNATURES" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">SIGNATURES</a></div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">TRADEMARKS</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#8220;</span>Ionis,&#8221; the Ionis logo, and other trademarks or service marks of Ionis Pharmaceuticals, Inc. appearing in this report are the property of Ionis Pharmaceuticals, Inc. &#8220;Akcea,&#8221; the Akcea logo, and other trademarks or service marks of Akcea Therapeutics, Inc. appearing in this report are the property of Akcea Therapeutics, Inc., Ionis&#8217; wholly owned subsidiary. This report contains additional trade names, trademarks and service marks of others, which are the property of their respective owners. Solely for convenience, trademarks and trade names referred to in this report may appear without the &#174; or TM symbols.</div>
<div><br /></div>
<div class="BRPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div>
</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
<div style="page-break-after: always;" class="BRPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
</div>
<div class="BRPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="BalanceSheet"><!--Anchor--></a><!--PROfilePageNumberReset%Num%3%%%-->IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONDENSED CONSOLIDATED BALANCE SHEETS</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in thousands, except share data)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Contracts receivable</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerAssetNetCurrent" id="Fact_42eb7b27d7ea459086945663ae763056" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,645</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerAssetNetCurrent" id="Fact_90c87b1639e7454d862938e1695fb4ba" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,896</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Inventories</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_bdc1851ec3a24426938e66ad4005713a" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,645</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other current assets</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current assets</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentNet" id="Fact_4cf8028d82514177b93946aa1df7c264" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">180,806</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentNet" id="Fact_5ad23e93b4e4467b9feec47f0d291fee" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">178,069</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patents, net</div></td>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeRelatedLiabilitiesCurrent" id="Fact_552968f4f2a9496e83f175a2ee89b95c" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">30,410</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_213f5a6701c24aa0979bad8e60ab97c3" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">88,560</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes payable</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedIncomeTaxesCurrent" id="Fact_2af0ce9cd98b44bd81fc94205bb5c219" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">16</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedIncomeTaxesCurrent" id="Fact_7acc385f5ade40c4a52676f52d77facb" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">36</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligationsExcludingConvertibleDebtCurrent" id="Fact_bfee8ed3f29a415ba60a766b5e0cc4b7" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,970</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesCurrent" id="Fact_b563c92d4e8b4add87b63f57c52a0e82" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">283,454</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term deferred contract revenue</div></td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermLoansFromBank" id="Fact_b3ea6b13b4de4225adb6586558c16a06" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">59,713</ix:nonFraction></div></td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total liabilities</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Liabilities" id="Fact_b675286a500340028e4203fe4698ca8a" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,827,610</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Liabilities" id="Fact_f7cd0990ec2c4e71bcb30f7b03262cba" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,839,953</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stockholders&#8217; equity:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common stock, $<span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockParOrStatedValuePerShare" id="Fact_89ceac2a6de84664a3444e0197c5952f" contextRef="c20211231" unitRef="U004" decimals="3" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockParOrStatedValuePerShare" id="Fact_81d34c4177db42eb9566a4ebacfe9a61" contextRef="c20220930" unitRef="U004" decimals="3" scale="0" format="ixt:num-dot-decimal">0.001</ix:nonFraction></ix:nonFraction></span> par value; <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_c1d115fce5ca4643b306e1dda169e403" contextRef="c20211231" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_967e3bfa845149deb2a16ff5f6733824" contextRef="c20220930" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">300,000,000</ix:nonFraction></ix:nonFraction></span> shares authorized, <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_7433a63c4a1045d2ab18a5f4dd2cfef3" contextRef="c20220930" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_aeabe9bc47984305a06e132d4d7bbbd3" contextRef="c20220930" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">142,017,411</ix:nonFraction></ix:nonFraction></span> and <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_16b1e67a7f564bfb8ebe67a950cecb91" contextRef="c20211231" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_987e70eb15fa4d6f8f4dee73a63054d5" contextRef="c20211231" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">141,210,015</ix:nonFraction></ix:nonFraction></span> shares issued and outstanding at <span style="text-indent: 0pt;">September 30, 2022</span> (unaudited) and <span style="text-indent: 0pt;">December 31, 2021</span>, respectively</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CommonStockValue" id="Fact_2ef68db29f344e1f9b9804fb82fc10d1" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">142</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CommonStockValue" id="Fact_b57e377e7b024f69a86bf33102ea3c25" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">141</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additional paid-in capital</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdditionalPaidInCapitalCommonStock" id="Fact_aebda853ea1647d1b274290dee09ac0f" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,034,554</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdditionalPaidInCapitalCommonStock" id="Fact_aee9cda9e03b48d4a74d89f28e31f6ec" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,964,167</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_5df551453918447e8a86ae46f488bc1a" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">63,140</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_ce487df6de7f42f7b8c77a08d145dc67" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">32,668</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RetainedEarningsAccumulatedDeficit" id="Fact_e5c1467d48e84e9db875c9a95c317d68" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,377,195</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
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  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
<div class="BRPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div>
</div>
<div style="page-break-after: always;" class="BRPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="BRPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="IncomeStatementQ2Q3"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in thousands, except for per share amounts)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0b7e92ae84094d37aed4349f19fe764e" contextRef="c20220701to20220930_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,647</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA revenue, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4f0d2ae9fede40368bb610a6f37f5eaa" contextRef="c20210101to20210930_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">115,321</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d86d3bacdddb400a9a8352d413fa6a37" contextRef="c20220701to20220930_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,107</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b69380d385c24da2911ecaae0873026f" contextRef="c20210701to20210930_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fe115db8a777437c817026804c674d7a" contextRef="c20220101to20220930_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">55,317</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_df7718a9917c4bc98606f70a48426e9c" contextRef="c20210101to20210930_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: 9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research and development revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fc7abdc8dfde471cb29faf8b3d03b1e5" contextRef="c20220701to20220930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">87,357</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d18c45e0616c4b608bc566221c7d5133" contextRef="c20210701to20210930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">48,273</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ea3d788d8e4c4ca49f0e56246a6353d6" contextRef="c20220101to20220930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">212,599</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_946194dd265d4cea91b3510e10eec2e5" contextRef="c20210101to20210930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">115,321</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7fb186405aa5453da2c9a3a77294b058" contextRef="c20220701to20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">159,767</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_1e995470a8934364abef7e0281a9272f" contextRef="c20210701to20210930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">133,093</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_37a5784739524a4d9d1eb2b56b0b5d5c" contextRef="c20220101to20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">435,478</ix:nonFraction></div></td>
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  <tr>
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  <tr>
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  <tr>
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  <tr>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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  <tr>
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  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;See accompanying notes.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
<div class="BRPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div>
</div>
<div style="page-break-after: always;" class="BRPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="BRPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="ComprehensiveLossQ2Q3"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in thousands)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_956abcf640b64e40a411493d69205818" contextRef="c20220701to20220930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">46,992</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unrealized losses on debt securities, net of tax</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Currency translation adjustment</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_e9b531ac4e7e466f809b4e8a0d95361e" contextRef="c20220701to20220930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">399</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Comprehensive loss</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
<div class="BRPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5</div>
</div>
<div style="page-break-after: always;" class="BRPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="BRPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="EquityQ1"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> EQUITY</span></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended&#xA0;September 30, 2021 and 2022</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Common Stock</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Stockholders</span>&#8217;</div></td>
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  <tr>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Paid in Capital</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Comprehensive Loss</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deficit</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Equity</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at <span style="text-indent: 0pt;">June 30, 2021</span></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_3a9555e88e8e4073b9ff1cc051b93040" contextRef="c20210630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">141,022</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_cfd0b9aef082475bb135e7948156a230" contextRef="c20210701to20210930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">490</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized losses, net of tax</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_11314cebb76149f4a608afac24ac04b8" contextRef="c20220701to20220930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_7b0eb56cbf6c4876adbb9cd78cb7fab3" contextRef="c20220701to20220930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign currency translation</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9.15pt; margin-left: 9.15pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_8046f4e57e4a427abdfdd14f900e96c9" contextRef="c20220701to20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">644</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at <span style="text-indent: 0pt;">September 30, 2022</span></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_0f0be876932540309deb6071f37c6b70" contextRef="c20220930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">142,017</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
<div class="BRPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6</div>
</div>
<div style="page-break-after: always;" class="BRPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="BRPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> EQUITY</span></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended&#xA0;September 30, 2021 and 2022</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Ionis</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Stockholders</span>&#8217;</div></td>
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  </tr>
  <tr>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Paid in Capital</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Comprehensive Loss</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deficit</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Equity</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_6356659201ed4d119c527a31f14dd229" contextRef="c20201231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">140,366</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_cf7e8cac0c644a7b91ce8d34fc742f71" contextRef="c20210101to20210930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_09f8d09c9d8c4d2c80eb0036946b4d91" contextRef="c20210101to20210930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_f499610f756c4e5784aa21bfb349b501" contextRef="c20210101to20210930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation" id="Fact_865184dac18a44e9ac95a25021cf9493" contextRef="c20210101to20210930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">276</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_b4b4d70b101d49b885e4f5fe3f5434f9" contextRef="c20210101to20210930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,285</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_1160e4ea51284b6596819627fd67f3f1" contextRef="c20210101to20210930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_dd5e8f4a865b4166bd45bd8834827a34" contextRef="c20210101to20210930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,285</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 4px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at <span style="text-indent: 0pt;">September 30, 2021</span></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_6a3ebbc8b51447a5952b335e52c85d67" contextRef="c20210930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">141,184</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_a4b9f22a573749a498a1e1f7668420b9" contextRef="c20210930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">141</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_6ef657a89a0c48fa84e86fffe91048f6" contextRef="c20210930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,942,348</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_4e98f97080bb4319bae0c10d29b9f45e" contextRef="c20210930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">530,536</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9.15pt; margin-left: 9.15pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation" id="Fact_cc4fc8ee6dcb408bb2e9fa76804ccd15" contextRef="c20220101to20220930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">331</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_6046e75faa184adbaecb97ff762c9034" contextRef="c20220101to20220930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_fd516e88077042dcbd5c3e223389cff5" contextRef="c20220101to20220930_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_55049b7b1f7545849462906bad3cf1ed" contextRef="c20220101to20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,217</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at <span style="text-indent: 0pt;">September 30, 2022</span></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_ab1b5a72d6704443ae923d4f7c3e7fc2" contextRef="c20220930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">142,017</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_303e394e05ca4145a59f47f98827626d" contextRef="c20220930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">142</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_6cf7c453ab9f4861bdff84a9bccec821" contextRef="c20220930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,034,554</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_d3438d70b67142c7a3a7bcc3fd453ffe" contextRef="c20220930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">63,140</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_e04b3c2d9b3b404ba5d9e43f14ca708e" contextRef="c20220930_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,377,195</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
<div class="BRPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div>
</div>
<div style="page-break-after: always;" class="BRPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="BRPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="CashFlows"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in thousands)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Depreciation</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Depreciation" id="Fact_8c77ba4be59247e38c94131c141d0abf" contextRef="c20210101to20210930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,665</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of right-of-use operating lease assets</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of patents</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfIntangibleAssets" id="Fact_edc8ad178aa7466a8d83a15fca3ea881" contextRef="c20220101to20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,805</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of premium on investments, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_246d1c45e9574034a56b56918f85ebb2" contextRef="c20220101to20220930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">9,072</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of debt issuance costs</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_0996ae3cb47d4deda2a70a7fe98905e0" contextRef="c20220101to20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,035</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss (gain) on investments</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Inventories</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInInventories" id="Fact_6cc57db037e24224babb23341491fa27" contextRef="c20220101to20220930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">4,161</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other current and long-term assets</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes payable</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounts payable</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInAccountsPayable" id="Fact_8a994583ad564784b70d134601567caf" contextRef="c20220101to20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,607</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued compensation</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued liabilities and other current liabilities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherCurrentLiabilities" id="Fact_08f6c9cf45f246f6a33cd0c9749cb737" contextRef="c20220101to20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">38,263</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherCurrentLiabilities" id="Fact_8da87902979a47b2b8cd9fcda264eef6" contextRef="c20210101to20210930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">19,526</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred contract revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_5d444769c22d417199294bd747e46936" contextRef="c20220101to20220930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">55,426</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_7536a4e7a5c548658c9c6c4190e7e76b" contextRef="c20210101to20210930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">71,610</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchases of short-term investments</div></td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of short-term investments</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchases of property, plant and equipment</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Acquisition of licenses and other assets, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchase of Bicycle Therapeutics plc common stock</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquireEquitySecuritiesFvNi" id="Fact_5df9fd70dbe646a0a3e7559fc71e19b8" contextRef="c20210101to20210930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,185</ix:nonFraction></div></td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net cash (used in) provided by investing activities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Financing activities:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from equity, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9.15pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_2013b605a8914f73b56ab03781e33c14" contextRef="c20210101to20210930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,285</ix:nonFraction></div></td>
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  </tr>
  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9.15pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchase of note hedges</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsForHedgeFinancingActivities" id="Fact_801427c3fed445c799493633b0f1efc9" contextRef="c20220101to20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9.15pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Principal payments on mortgage debt</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInFinancingActivities" id="Fact_af5d9d765265424f939925e68f5a2822" contextRef="c20210101to20210930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">308,423</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net (decrease) increase in cash and cash equivalents</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_695ef20670484629abffb58a97885612" contextRef="c20210101to20210930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">235,289</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash and cash equivalents at beginning of period</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_f005ffe7399e4372b86484b39e4de899" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">869,191</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
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<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
<div><br /></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Notes"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">NOTES TO CONDENSED CONSOLIDATED FINANCIAL STATEMENTS</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30, 2022</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.&#160; Basis of Presentation</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended&#xA0;September 30, 2022 and 2021 on the same basis as the audited financial statements for the year ended December 31, 2021. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2021 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;).</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2.&#160; Significant Accounting Policies</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue Recognition</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Our Revenue Sources</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts within deferred revenue in our condensed consolidated balance sheet.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808. ASC 808 does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC 606, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span>. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We also recognize sales milestone payments and royalties we earn under our other partnerships as commercial revenue.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaborative agreements</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, research and development, or R&amp;D, services, and manufacturing services.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 6, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for collaborations with substantive changes that occurred in 2022. Additionally, see </span>Note 6, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2021 for a summary of each of our material collaborative agreements.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">1.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Identify the contract</div></td>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partner approved the contract and we are both committed to perform our obligations;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have identified our rights, our partner&#8217;s rights and the payment terms;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and</div></td>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe collectability of the consideration is probable.</div></td>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Identify the performance obligations</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Often we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.</div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">3.</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Determine the transaction price</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/or are usually based on scientific progress which is inherently uncertain. For example, in the first quarter of 2022, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c66a5241a21143ed8f3a497ac21b877d" contextRef="c20220101to20220331_ProductOrServiceAxis_Ion859Member_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">10</ix:nonFraction> million milestone payment from Biogen when Biogen advanced the Phase 1/2 study for ION859, an investigational antisense medicine targeting leucine rich repeat kinase 2, or LRRK2, in patients with Parkinson&#8217;s disease. We did not consider the milestone payment probable until Biogen achieved the milestone event because advancing ION859 was contingent on Biogen advancing a Phase 1/2 study and was not within our control. We recognized the milestone payment in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payment.</div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">4.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Allocate the transaction price</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Next, we allocate the transaction price to each of our performance obligations. When we have to allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated future product sales;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated royalties we may receive from future product sales;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated contractual milestone payments we may receive;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated expenses we may incur;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated income taxes; and</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A discount rate.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We typically estimate the selling price of R&amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated number of internal hours we will spend performing these services;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work we will perform;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work that we will contract with third parties to perform; and</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of API we will use.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Recognize revenue</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize royalty revenue, including royalties from SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;A, expenses in our condensed consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Reserves for TEGSEDI and WAYLIVRA commercial revenue</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi, Sobi is responsible for any applicable reserves.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Prior to our distribution agreements with Sobi, w</span>e recorded TEGSEDI and WAYLIVRA commercial revenue at our net sales price, or transaction price. We included in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offered within contracts between us and our customers, wholesalers, distributors, health care providers and other indirect customers. We estimated our reserves using the amounts we have earned or we could claim on the associated sales. We classified our reserves as a reduction of accounts receivable when we were not required to make a payment or as a current liability when we were required to make a payment. In certain cases, our estimates included a range of possible outcomes that were probability weighted for relevant factors such as our historical experience, contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflected our best estimates under the terms of our respective contracts. When calculating our reserves and related TEGSEDI and WAYLIVRA commercial revenue, we only recognized amounts to the extent that we considered it probable that we would not have to reverse a significant amount of the cumulative sales we previously recognized in a future period. Under our agreements with Sobi, we transferred all reserves to Sobi. See our revenue recognition policy in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span>, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2021 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales prior to our agreements with Sobi.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Research and development revenue under collaboration agreements:</span></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Upfront payments</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we enter into a collaboration agreement and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. For example, under our collaboration agreement with Roche to develop IONIS-FB-L<sub>Rx</sub> for the treatment of complement-mediated diseases, we received a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_72588160d9344e3d91319fe6a66f7d24" contextRef="c20181001to20181231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">75</ix:nonFraction> million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_df2e1cb511f24d2a84b6cc2d7d4dc617" contextRef="c20181001to20181231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">75</ix:nonFraction> million upfront payment using an input method over the estimated period of time we are providing R&amp;D services.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the second quarter of 2022, we achieved a $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPriceAdditions" id="Fact_daa95f02868e4437b7a4942ad80e12fa" contextRef="c20220401to20220630_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">20</ix:nonFraction> million milestone payment from Roche when we advanced the Phase 2 study in patients with dry age-related macular degeneration, or AMD, under our collaboration agreement with Roche to develop IONIS-FB-L<sub>Rx</sub>. We added this payment to the transaction price and allocated it to our R&amp;D services performance obligation for IONIS-FB-L<sub>Rx</sub>. We are recognizing revenue related to this milestone payment over our estimated period of performance. As a result, we recorded a cumulative catch-up adjustment of $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5e4a2ac5cea0453ea0628fc5888bb5c0" contextRef="c20220401to20220630_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">13.8</ix:nonFraction> million to increase revenue in the second quarter of 2022 for this payment. We estimate we will satisfy our performance obligation in the fourth quarter of 2023.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2022, we recognized $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ec2c8525a42c4b9eba9f0832f0b07e2b" contextRef="c20220701to20220930_TypeOfArrangementAxis_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">13</ix:nonFraction> million in milestone payments when Biogen advanced <ix:nonFraction name="ions:NumberOfTargetsAdvanced" id="Fact_f2258c9c40f845b4bb100ba3ef3051b5" contextRef="c20220701to20220930_TypeOfArrangementAxis_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> targets under our neurology collaborations. We concluded that these milestone payments were not related to our R&amp;D services performance obligations for these collaborations. Therefore, we recognized the milestone payments in full in the third quarter of 2022.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">License fees</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. For example, in the third quarter of 2022, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7748c0a72a8d4a139b8a38244868c144" contextRef="c20220701to20220930_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction> million license fee from Roche when Roche licensed IONIS-FB-L<sub>Rx</sub>, an investigational medicine in development to treat complement-mediated diseases.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Sublicense fees</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not have any performance obligations related to the sublicense. For example, in the fourth quarter of 2020, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d95ecd0c2d0e4ea494c6592f2153d064" contextRef="c20201001to20201231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">41.2</ix:nonFraction> million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Amendments to Agreements</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:</div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the goods and/or services are sold at a stand-alone selling price.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Multiple agreements</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the agreements were negotiated together with a single objective;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the goods and/or services promised under the agreements are a single performance obligation.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, in the second quarter of 2018, we entered into <ix:nonFraction name="ions:NumberOfAgreementsWithCollaborationPartner" id="Fact_c0d9a811936e47c2b113f70412abe1a4" contextRef="c20180401to20180630_MajorCustomersAxis_BiogenIncMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> separate agreements with Biogen at the same time: a new strategic neurology collaboration agreement and a stock purchase agreement. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Eplontersen Collaboration with AstraZeneca</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_53da6e65fb0741c483420c0238104ade" contextRef="c20210101to20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction> million upfront payment in 2021.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our eplontersen collaboration under ASC 808 and identified <ix:nonFraction name="ions:NumberOfMaterialComponents" id="Fact_b27e54c14e90416580647f971d492180" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a result we had <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_e8e1aec533f84dbf98a2133cce0f7dc7" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation.&#160; For our sole performance obligation, we determined the transaction price was the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_387a94400e2542adb3feef5e16cbd22c" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction> million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is responsible for <ix:nonFraction name="ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" id="Fact_3165c6664dcc46f6bd3fb9a729593495" contextRef="c20220101to20220930_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">55</ix:nonFraction> percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#8217;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related to commercial and medical affairs activities as reductions of our SG&amp;A expense and R&amp;D expense, respectively. Refer to Item 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations</span>, for further details on the financial statement impacts of our eplontersen collaboration with AstraZeneca. </div>
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<div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents the amounts we have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts receivable to be unconditional. We typically receive payment within </span><span style="-sec-ix-hidden:Fact_cb46feec840d4d05b86df2a2af3b44c3">one quarter</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of billing our partner or customer</span>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of September 30, 2022, approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_ddb9c9779caa4c7ba7a8628627b81f91" contextRef="c20220101to20220930_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">73.1</ix:nonFraction> percent of our contracts receivables were from <ix:nonFraction name="ions:NumberOfSignificantCustomers" id="Fact_1a88c8e3635d4a64afd7542090bb8bb4" contextRef="c20220101to20220930" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> significant customers. As of December 31, 2021, approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_2797753f496a4c3a9e250ecbc9db8bec" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">93.8</ix:nonFraction> percent of our contracts receivables were from <ix:nonFraction name="ions:NumberOfSignificantCustomers" id="Fact_61c499808edf4f65970284a4fd7b4782" contextRef="c20210101to20211231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> significant customers.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled SPINRAZA Royalties</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen for SPINRAZA royalties. We include these unbilled amounts in other current assets on our condensed consolidated balance sheet.</div>
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<div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers and receive payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue on our condensed consolidated balance sheet.</span> During the three months ended&#xA0;September 30, 2022 and 2021, we recognized $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_a6fb915664d048758471b4263bdbfedd" contextRef="c20220701to20220930" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">23.1</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_8467a8264e824b68904b44a564361380" contextRef="c20210701to20210930" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">21.1</ix:nonFraction> million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">During the </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recognized $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_5f0eaf8c9d8c408da05cc1e442f052d3" contextRef="c20220101to20220930" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">69.8</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_51a5fbfebaa247199fd1c1ee337783af" contextRef="c20210101to20210930" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">71.9</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. </span>For further discussion, refer to our revenue recognition policy above.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Sales</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales. </div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our accrued liabilities consisted of the following (in thousands):</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30, 2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2021</div></td>
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    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Clinical development expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AccruedClinicalDevelopmentExpenses" id="Fact_9fa65e9eb4874e529d2b5a8558dbeefc" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">103,635</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Estimated Liability for Clinical Development Expenses</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly basis, we estimate our liability for preclinical and clinical development expenses we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these expenses. These expenses primarily relate to third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon settlement, these expenses may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, Cash Equivalents and Investments</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#8220;available-for-sale&#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our condensed consolidated statement of operations. We use the specific identification method to determine the cost of securities sold.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At September 30, 2022, we held equity investments in <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_8037e90f29fb43ae9797ff009a688387" contextRef="c20220930" unitRef="U010" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> publicly held companies and <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_e003aeab75174162b833cf14b3a44106" contextRef="c20220930" unitRef="U010" decimals="INF" scale="0" format="ixt-sec:numwordsen">eight</ix:nonFraction> privately held companies.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our condensed consolidated statement of operations. We account for our equity investments in publicly held companies based on observable inputs such as quoted prices in active markets for identical assets. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. We recorded an immaterial amount of fair value adjustments related to our equity investments for the three and nine months ended&#xA0;September 30, 2022 and 2021.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or net realizable value under the first-in, first-out method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials, they have alternative future uses, which we refer to as clinical raw materials. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency. Our raw materials - commercial inventory includes API for our commercial medicines. We capitalize material, labor and overhead costs as part of our raw materials - commercial inventory.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryRawMaterials" id="Fact_e3f1efde1cdb414796dec720e17eac54" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,646</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryWorkInProcess" id="Fact_182d548d120f4e1daae74044c3e1bbe5" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,770</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryFinishedGoods" id="Fact_b21c128f10e14f89b4963ecd92676ea1" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">288</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryFinishedGoods" id="Fact_70a3a016ecb849cd9021230823cf224d" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">390</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;"><div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_6f6a7ebaae1b4d95ace7fcfcf1fba210" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,645</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_3e4c02edf53745679ae7e698216e7837" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">24,806</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine if an arrangement contains a lease at inception of the arrangement. As of September 30, 2022, we only had operating leases. We recognize a right-of-use operating lease asset and associated short- and long-term operating lease liability on our condensed consolidated balance sheet for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we will pay over the lease term. We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal options if we concluded we were reasonably certain that we will exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease term.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commenced in January 2022 when the office space was ready for our tenant&#8217;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending in November 2028 with no option to extend the sublease. Under the sublease agreement we provided a <ix:nonNumeric name="ions:LessorOperatingLeaseFreeRentPeriod" id="Fact_47d0951dc5cf46abb2ab61b44a977bad" contextRef="c20220101to20220930_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceInBostonMassachusettsMember" format="ixt-sec:durwordsen">seven-month</ix:nonNumeric> free rent period, which commenced in January 2022. We will receive lease payments over the sublease term totaling $<ix:nonFraction name="us-gaap:LessorOperatingLeasePaymentsToBeReceived" id="Fact_6e9e11d907a042dcbbbf9300319016c9" contextRef="c20220930_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceInBostonMassachusettsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">9.6</ix:nonFraction> million. We are recognizing sublease payments as other income on a straight-line, gross basis over the term of our sublease.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility in Oceanside, California. The lessor will develop and construct a building composed of manufacturing space, office space, research and development space and warehouse space. We will design and construct tenant improvements to customize the facility&#8217;s interior space. We will lease the facility for an initial term of <span style="-sec-ix-hidden:Fact_f55efb1442234cfa8ea3fb7d8884b511">20 years and 3 months</span> with options to extend the lease for <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_760c2b88dc0d481e88f2d0e0c8d19af9" contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> additional terms of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_f6b3b6f9036a4d40a51e0a3f01a6c666" contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember" format="ixt-sec:duryear">10</ix:nonNumeric> years each. The lease will commence when the lessor's construction is complete and we are able to occupy the facility.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we concurrently entered into <ix:nonFraction name="ions:NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" id="Fact_3a09e1ebe9164652832dfa06144761b6" contextRef="c20221001to20221031_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> purchase and sale agreements with a real estate investor. Under the agreements, we sold and leased back the facilities at our headquarters location in Carlsbad, California and will sell, subject to meeting certain closing conditions, <ix:nonFraction name="ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" id="Fact_fe0b2942ef0a4776b1bcf49ba82fcb2d" contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_LandMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> lots of undeveloped land adjacent to our headquarters. We sold the facilities at our headquarters for a total purchase price of $<ix:nonFraction name="us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_8281e5fe1022475983c06c0c19ae0e83" contextRef="c20221001to20221031_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">263.4</ix:nonFraction> million and we expect to receive total proceeds of $<ix:nonFraction name="us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_b72d83b519a34120a79d42b97f4bb816" contextRef="c20221001to20221031_PropertyPlantAndEquipmentByTypeAxis_LandMember_StatementScenarioAxis_ScenarioForecastMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">33.0</ix:nonFraction> million upon the close of the sale of the <ix:nonFraction name="ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" id="Fact_2d9295561e1746c093f8cdc68e0c9622" contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_LandMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> lots. We used a portion of the sale proceeds to extinguish our mortgage debt on our headquarters facilities of $<ix:nonFraction name="us-gaap:RepaymentsOfSecuredDebt" id="Fact_ef1168c278694b4490a5b679d4b1070c" contextRef="c20221001to20221031_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">51.3</ix:nonFraction> million. The initial lease term for our headquarters facilities is <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_39a9279e3c6d4f3fbe9afec67e73b36a" contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember" format="ixt-sec:duryear">15</ix:nonNumeric> years with options to extend the lease for <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_6c173c46df574b918c15a7694914e33d" contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> additional terms of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_de4bb5146b8c49379bf250eefecd6af9" contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember" format="ixt-sec:durwordsen">five years</ix:nonNumeric> each. In connection with the sale of our <ix:nonFraction name="ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" id="Fact_0feae749ec5e4b4bbcb200fe0a289143" contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_LandMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> undeveloped lots, we will enter into a build-to-suit lease agreement with the same real estate investor who will build a new R&amp;D facility for us on those lots. Once this new facility is completed, our lease will commence.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Patent Expenses</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our condensed consolidated balance sheet and we expense them as the services are provided.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the U.S. Patent and Trademark Office, or foreign equivalent, issues the patent. </span>We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes. Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the provision for income taxes in the period in which we make such determination.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Long-lived Assets</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate long-lived assets, which include property, plant and equipment, right-of-use assets and patent costs, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Use of Estimates</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the </span>U.S. that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Loss Per Share</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our basic net loss per share for the three and nine months ended&#xA0;September 30, 2022 and 2021 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Our basic net loss per share for the three months ended September 30, 2022 and 2021 were $<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_aab817918ee7462eafc4e0247e0ea5c8" contextRef="c20220701to20220930" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.33</ix:nonFraction> and $<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_af00e59c7e2a4e16b91a7293788669b4" contextRef="c20210701to20210930" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.58</ix:nonFraction>, respectively. Our basic net loss per share for the nine months ended&#xA0;September 30, 2022 and 2021 were $<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_8d02913bc72348c4afaea5d029066c53" contextRef="c20220101to20220930" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">1.53</ix:nonFraction> and $<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_8574d7638db8427d9c1c26a77e307fb9" contextRef="c20210101to20210930" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">1.80</ix:nonFraction>, respectively.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Diluted net loss per share</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three and nine months ended&#xA0;September 30, 2022 and 2021, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:</div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4aaf64389f424f1a8094aeb84078d413" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8dfff05be34d436c9d4d1390c53656fd" contextRef="c20210930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction> percent convertible senior notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_173edf309e3e40a2ad0d382e948465e6" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_80e4d24ab8f24b0d9a90368e65b06be6" contextRef="c20210930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction>% Notes;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9a0dc9452934497c9f42b18776b705fa" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b4b26c4a179d451fa08fce52719b1c35" contextRef="c20210930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction>% Notes;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e04081c13bbe48d3bb9b3d0cca81d860" contextRef="c20210930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_eccc4161cecb4e0e9bd2f79ccde27795" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction> percent convertible senior notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2d011315162b43398edc4d43f61dfe90" contextRef="c20210930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_040223863f694143aeafc77acbcabb62" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction>% Notes;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_00ed48c13a3e41a59f57e78e32a2e336" contextRef="c20210930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5765a5913d9b40179d92f2285226cd54" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction>% Notes;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested performance restricted stock units, or PRSUs; and</div></td>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Stock Purchase Plan, or ESPP.</div></td>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three and nine months ended&#xA0;September 30, 2021, common stock that we could have issued from our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7f6b5843a1514609ba42abde6c581d38" contextRef="c20210930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction> percent convertible senior notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_d1475e898f8645c5bb5ab96fa37efd40" contextRef="c20210930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes, would also have had an anti-dilutive effect on net loss per share.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally as of September 30, 2022, we had warrants related to our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2ad3f2367557405a8c6d2324e912a59a" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_abddc1cdda9749a6b8af5dd8ac5eb3c8" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Derivatives and Hedging</span>, or ASC 815, and our convertible debt instruments were not issued at a substantial premium. We record the entire debt issuance costs as a contra-liability in our condensed consolidated balance sheet at issuance and we amortize them over the contractual term using an updated effective interest rate. As such, the ending balances for our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fa35c62ae15545fda47bd92f0ec9050d" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dfae12bf8c0d4b1fa86a0ad27d83e519" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes represent the principal balance of each convertible debt instrument less debt issuance costs. We amortize debt issuance costs for our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4104add5953b45b09004aee6e573d81f" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_23f33708bb144c8896edb768bcc0da12" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes over the respective contractual term using an effective interest rate of <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_1f8672f0057c4cd3ba9ee1a3d610959e" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_63df7b45bec94d108f6f2369726dcb1c" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.5</ix:nonFraction></ix:nonFraction> percent for each note. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Convertible Debt</span>, for further details on our convertible debt instruments.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Call Spread</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the issuance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2de199144db84606922afa28c32d16ec" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f0716a76728945aeacfc77c73b2d1ec7" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not meet the definition of a liability using the guidance contained in ASC Topic 480, therefore we account for the note hedges and warrants using the Derivatives and Hedging &#8211; Contracts in Entity&#8217;s Own Equity accounting guidance contained in ASC 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified in shareholders&#8217; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our condensed consolidated balance sheet. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Segment Information</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We operate as a <span style="-sec-ix-hidden:Fact_ba6a4e8bb35940dbbf919d263b57d70e">single</span> segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-based Compensation Expense</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On the grant date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the awards, and actual and projected employee stock option exercise behaviors.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or 2020 Plan. As a result, all employees are now under an Ionis stock plan and subject to the same Black-Scholes assumptions.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the nine months ended&#xA0;September 30, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">*</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_74bbbb57209c4f53960b9d7c3438ee6b" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_b2ac901653d54e2fadb1e34420e76d70" contextRef="c20220101to20220930_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_658bc4cd50024cbc9d7a903e428fbe7f" contextRef="c20220101to20220930_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" format="ixt-sec:durwordsen">ten years</ix:nonNumeric> for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the nine months ended&#xA0;September 30, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns. </ix:footnote></div></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Board of Director Stock Options:</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">ESPP:</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RSU&#8217;s:</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_27893998ace24d7cb0e5fa8a728fcf92" contextRef="c20220101to20220930_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_0b9e4755a19545e988f3c011792dba0c" contextRef="c20220101to20220930_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember_RangeAxis_MaximumMember" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. The RSUs we granted after June 2020 to our board of directors fully vest after <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_6ad8053af26d4d419b4294b9cd273b8f" contextRef="c20220101to20220930_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember_RangeAxis_MinimumMember" format="ixt-sec:durwordsen">one year</ix:nonNumeric>. The weighted-average grant date fair value of RSUs granted to employees and our board of directors for the nine months ended&#xA0;September 30, 2022 were $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_7654fd0b1d374d55b0c76914d3cd1ad7" contextRef="c20220101to20220930_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">34.88</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_82a83a2536174d579407e5d513b7a99f" contextRef="c20220101to20220930_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">38.06</ix:nonFraction> per share, respectively.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PRSU&#8217;s:</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added PRSU awards to the compensation for our other Section 16 officers. Under the terms of the grants, <span style="-sec-ix-hidden:Fact_3ea144f70898401099a1731ad0c7e39f"><span style="-sec-ix-hidden:Fact_b531c97d5a394e3f8a5454ecd82ddb93"><span style="-sec-ix-hidden:Fact_b2b6dbe875764e78b9cce0b8464216dd">one third</span></span></span> of the PRSUs may vest at the end of <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" id="Fact_22182278d2c74c399b1aa1ec24dcb90a" contextRef="c20220101to20220930_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U014" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> separate performance periods spread over the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_eaaa26558fcd4695b1458629faf19186" contextRef="c20220101to20220930_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" format="ixt-sec:durwordsen">three years</ix:nonNumeric> following the date of grant (i.e., the one-year period commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" id="Fact_a18106d46f494438a0e064c9f9a96fbd" contextRef="c20220101to20220930_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U001" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_2200a3292de944e78e0d6c8d840bacb1" contextRef="c20220101to20220930_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MinimumMember" unitRef="U003" decimals="INF" scale="-2" format="ixt-sec:numwordsen">zero </ix:nonFraction>percentto <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_ce7480294faa46eab25c9b702916942c" contextRef="c20220101to20220930_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">150</ix:nonFraction> percent of the target number depending on our relative TSR.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to our Section 16 officers for the nine months ended&#xA0;September 30, 2022 and 2021 were $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_f686380f406d44659451af43ea4a98c6" contextRef="c20220101to20220930_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">42.28</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_f37b71af46f844b7971b1a2b89993315" contextRef="c20210101to20210930_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">77.17</ix:nonFraction> per share, respectively.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the three and nine months ended&#xA0;September 30, 2022 and 2021 (in thousands).</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_cfcae472d24a41eba5315fc58eb907e1" contextRef="c20220101to20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">74,575</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_6f949baf6d1140d588b155609b49e954" contextRef="c20210101to20210930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">98,419</ix:nonFraction></div></td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of September 30, 2022, total unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" id="Fact_6ffe2ab146ea4bd888ad8a1bb3fc3738" contextRef="c20220930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">50.9</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_221a3013ba19446cad9c335f9391fa1a" contextRef="c20220930_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">53.0</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_1a5a87c9d0c04b5799a90b3d2965c63f" contextRef="c20220930_AwardTypeAxis_PerformanceSharesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.4</ix:nonFraction> million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures. We expect to recognize the cost of stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_13a68deb2d8d496a9b99b31f4abcfe12" contextRef="c20220101to20220930_AwardTypeAxis_EmployeeStockOptionMember" format="ixt-sec:duryear">1.2</ix:nonNumeric> years, <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_94356ff2a4564b669110ba6365630dc9" contextRef="c20220101to20220930_AwardTypeAxis_RestrictedStockUnitsRSUMember" format="ixt-sec:duryear">1.4</ix:nonNumeric> years and <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_715166969b8f40d5bb56857e5eca4ce6" contextRef="c20220101to20220930_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:duryear">1.1</ix:nonNumeric> years, respectively. Our stock-based compensation expense related to equity awards decreased in the three and nine months ended September 30, 2022 compared to the same periods in 2021 due to decreased headcount of longer-tenured employees as a result of restructuring our commercial operations for TEGSEDI and WAYLIVRA.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Recently Adopted Accounting Standards</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2022, the Financial Accounting Standards Board, or FASB, issued clarifying guidance on fair value measurement of equity securities subject to contractual trading restrictions. The guidance clarifies that contractual trading restrictions are not considered part of the unit of account of equity securities and therefore, are not considered when measuring the fair value of equity securities. This update is effective for interim and annual periods beginning January 1, 2024 on a prospective basis. Early adoption of this guidance is permitted at an interim or annual period. We early adopted this new guidance in the third quarter of 2022. This guidance did not have an impact on our condensed consolidated financial statements.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any other recently issued accounting standards to have a material impact to our financial results.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3.&#160; Investments</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2022:</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" id="Fact_8cd01e7f5688446294ec6f1b2d7e38df" contextRef="c20220930" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">3</ix:nonFraction></div></td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" id="Fact_6217a171f5784696968b178278e97ffa" contextRef="c20220930" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction></div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As illustrated above, at September 30, 2022, <ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" id="Fact_ecfa1cb8a4484b48a192e8436b1431fe" contextRef="c20220930" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">97</ix:nonFraction> percent of our available-for-sale securities had a maturity of less than <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_34c87d75876e42c988ffebc06f56b6a3" contextRef="c20220101to20220930" format="ixt-sec:durwordsen">two years</ix:nonNumeric>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All of our available-for-sale debt securities are available to us for use in our current operations. As a result, we categorize all of these securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date. This reflects our intention to use the proceeds from the sale of these investments to fund our operations, as necessary.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We invest in available-for-sale securities</span> with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard &amp; Poor&#8217;s, or S&amp;P, Moody&#8217;s or Fitch, respectively.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At September 30, 2022, we had an equity ownership interest of less than 20 percent in <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_b7edbc55e46842cb916a4ced56279788" contextRef="c20220930" unitRef="U010" decimals="INF" scale="0" format="ixt-sec:numwordsen">eight</ix:nonFraction> private companies and <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_8144a98eb4174391a5f3065f3f804da4" contextRef="c20220930" unitRef="U010" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> public companies with which we conduct business.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>
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<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Available-for-sale securities:</span></div></td>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_7842515e18104a5cafcff84ddb01d951" contextRef="c20220930_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">487,666</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_17f5c15fd8fe452b890ee866cfaa6b85" contextRef="c20220930_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">462,475</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_48196ae3d4df4f8195e5c9e5179b69ee" contextRef="c20220930_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,964</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_3e165eb36915445a94e7bca3626be047" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,133,227</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_3c026731cf6c4d2c9f3bb6487eb52874" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">35</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_cbaf34a8cf1344ed8d1c9bd3764052c6" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,647</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_401ef7ec0ee84b33b734c6646f73945d" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,121,615</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_e739ce406a594fdab205b3f709378b35" contextRef="c20220930_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">258,362</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_1465e0f748cd4bfaa10d9f2bc25757c3" contextRef="c20220930_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_28d6823308c14eabb012545df1bbf47e" contextRef="c20220930_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,654</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_dff0a77ea162428eac31903b7ae1af1c" contextRef="c20220930_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">245,714</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_4069992e62e44ec39ab5806e1ac879fa" contextRef="c20220930_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,987</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_13b8b3118986468c94cef784db3d7d85" contextRef="c20220930_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_8c034ba7ebd94e519637bf63e04e1b9f" contextRef="c20220930_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,541</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_907c5df34a09413bb109221fad1ea266" contextRef="c20220930_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,454</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_e43e28c5271b42a889a3b5a4967cc28d" contextRef="c20220930_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">298,431</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_9945c8a3aa274e52aa7dfeabc6567ab4" contextRef="c20220930_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,591</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_2b2ee63d727e423482b317c18a37ce81" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">600,371</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_22456af2bd1a42a5aaa84149b3a6373e" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">29</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_3f93907b739e4f8a80f71070bbbc98e2" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,982</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_33930b14001f46ccb9bf26b44f06a253" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">579,418</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_c63efe923e13426992c34154ca0ceb66" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,733,598</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_4d9475d7048b443985ccf0e54c482dde" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">64</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_abe680e773e045d898d7e780327a8001" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,629</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_ed64a9779a3842959199d38607dc68f6" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,701,033</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (2)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_795298199a7149089987fd608d910788" contextRef="c20220930_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,097</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_95a1e63d6d4c49f48092f55cc7344a6f" contextRef="c20220930_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_720e14f204184668ac412128829c1d4c" contextRef="c20220930_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,841</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_c9668cdfca24444facba84f5586a8b21" contextRef="c20220930_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,256</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Privately held equity securities included in deposits and other assets (3)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_642c9681829a411280b706605512aec4" contextRef="c20220930_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">23,115</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_10dc545d20404abda7146b5a706c0e00" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">47,628</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div></td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_a65f661f76de418c8ded0d80f7684b50" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">345</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_d8f9bd55d10c46e8a7923b828bf66f7b" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">638,615</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_9edb30f88d124e4f98e5fc6733baa317" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">471</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_35b1772ea2884933bfa48eab5441097a" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,966</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_bd78e79378ff4eecb24ada86ee7d4685" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">635,120</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_d8842e093daf4aa8a441e191da86ea99" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,251,172</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_4a16a27e0c4144fea9d33948c111d40b" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,263</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_5d60bf6074c241728013af9aebe4f553" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,311</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_282a1da5440143508a579978a45d2601" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,248,124</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_b8a712e5f4af42cdb9018ff5937f5e79" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,897</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_8b35758c336d4c378e03fdeaeaa046d7" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,145</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_8bd47c89fd1645cfa78adda562a9364e" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">50,527</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_f7a5c21d883b40c784a842b4eab86b9d" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,115</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_bf106be9d5824af3aa9e4c635557fb8a" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,148</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_ecad1868d9ae4c4cb68ebd3c78a85d30" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,298,651</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_2ec4116852e041e3a2a38cb16ff4ea22" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Includes investments classified as cash equivalents in our condensed consolidated balance sheet.</ix:footnote></div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_20cf8a92586d4d88bc45b040cb662025" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Our equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the nine months ended&#xA0;September 30, 2022, we recognized a $<ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_3313864190a543a6b47d32b6b504a1c9" contextRef="c20220101to20220930_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.9</ix:nonFraction> million unrealized non-cash loss in our condensed consolidated statement of operations related to a decrease in the fair value of our investments in publicly traded companies.</ix:footnote></div></td>
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<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_55aad856d839435daad2d772a2ea1bc5" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at</span> cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></ix:footnote></div></td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments we consider to be temporarily impaired at September 30, 2022 (in thousands, except for number of investments).</div>
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<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 12 Months of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Temporary</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impairment</div></td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Investments</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_333cdd7221c74a659058428cb96f027e" contextRef="c20220930_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U015" decimals="0" scale="0" format="ixt:num-dot-decimal">397</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_2e0cac4f3e6445e4af1d421cd8ba2264" contextRef="c20220930_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">591,245</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_903a58d3bf3c421b9166ac1d0a37f22d" contextRef="c20220930_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,897</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_183b7171ce6948fe93c1afb5708dc040" contextRef="c20220930_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">133,763</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_2bc4f2d4d6bd455e9474ce6348458023" contextRef="c20220930_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,084</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_39ca68f5ced34e02a3fb7f209ed77346" contextRef="c20220930_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">725,008</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_6a521c4aea4b4d6186a40cc4ac11ef16" contextRef="c20220930_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,981</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 16%; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_f82ef35b85bc4b76a2ca3ea408acca74" contextRef="c20220930_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U015" decimals="0" scale="0" format="ixt:num-dot-decimal">31</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_0a9f0760b76943a0bb457df5aa11d275" contextRef="c20220930_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">69,640</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_a606df5dbef24526ade176d96aa0c07b" contextRef="c20220930_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">875</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_2d0505e6d78b437083a13a36af9d0e35" contextRef="c20220930_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">53,299</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_be6630f1d422413eb69c31e0abbb4c84" contextRef="c20220930_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,352</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_9e4b0d43d3f14d11b3cdc492ef07dd02" contextRef="c20220930_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">122,939</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_eba3f72c498e466687adcba61f086b48" contextRef="c20220930_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,227</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_2e46b5062fb3478c908336d6d2d994c6" contextRef="c20220930_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U015" decimals="0" scale="0" format="ixt:num-dot-decimal">74</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_392a47ad8b314b019fde0f086884f91a" contextRef="c20220930_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">643,231</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_b473b5a2bf6f472895d5dbf195a86994" contextRef="c20220930_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,327</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_1ee53f584ab24cb6b581f7eae1eba196" contextRef="c20220930_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">21,769</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_98453b0c0b144bba86ec994206fdc1cb" contextRef="c20220930_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">679</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_4d01726992bb4d94b31e50877ad828f0" contextRef="c20220930_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,929</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_401d55f983434e8d9399ad8c2fc7758d" contextRef="c20220930_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,337</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_a21f49784eae40489b0406c92c97e44e" contextRef="c20220930_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U015" decimals="0" scale="0" format="ixt:num-dot-decimal">2</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_ed6918e8de4a4cddb68b84b0973ef21c" contextRef="c20220930_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">994</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_eb8bb8a7eb794fd2aa573bebbef50d6c" contextRef="c20220930_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_fe22a62f0cae44359a1087d8ba07f963" contextRef="c20220930_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,970</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_e7162ed2803b4dcdb16f05d3cdc01bed" contextRef="c20220930_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">64</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_f5242826454a4306b595db9815050842" contextRef="c20220930_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,964</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_378bb0ac33e34dfdbe5d8fb3bf1f7047" contextRef="c20220930_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">76</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_7e1f0b8e65b4437a89df6913266edd37" contextRef="c20220930" unitRef="U015" decimals="0" scale="0" format="ixt:num-dot-decimal">644</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_a321ec73c6744478ab33de1911123ebf" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,345,270</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_32652639154d4153a0f3bf2d89e86160" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,769</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_c18b9c577f3c4038843a9b7ee496d0d4" contextRef="c20220930" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">266,568</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase rather than underlying credit deterioration for any of the issuers. We believe it is more likely than not that we will be able to hold our debt securities with declines in value to maturity. Therefore, we anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4.&#160; Fair Value Measurements</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1, defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly held biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions, which includes our investments in equity securities in privately held biotechnology companies. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at September 30, 2022 and December 31, 2021 that we regularly measure and carry at fair value. As of December 31, 2021, one of <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">our investments in publicly held biotechnology companies was subject to trading restrictions that ended in the third quarter of 2022; as a result, we included a lack of marketability discount in valuing this investment, which is a Level 3 input.</span> The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_63265628852a4ba29e93a651719977ed" contextRef="c20220930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (4)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_c11eb07ea3324e24902d31be146e2aba" contextRef="c20220930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">85,315</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_4256bb9f94cb424da59655cd85ab7f9f" contextRef="c20220930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (3)</div></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_5a3e302889e04832960498aaf3fc8b2b" contextRef="c20220930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,964</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_c79df577c73b4e58b8a6ebc687660780" contextRef="c20220930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_0dfa9dad994240f3bfc133e3f1806e42" contextRef="c20220930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,964</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_d9283a639225417ab2226e23faf78f90" contextRef="c20220930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets</div></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_345ac2114958402e8c0526123b413533" contextRef="c20220930_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,256</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_49579a46ef144e9db6adc23b832e2254" contextRef="c20220930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,256</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_714e6b6bc417487db0580f5a9df0b246" contextRef="c20220930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_d0a6389d73c44d39b4f347873c5b2f28" contextRef="c20220930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px;"><div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_9623b6fc811d446d8de6fe8c0a84d07a" contextRef="c20220930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,940,249</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_5e3adc88dc374a21be5199cc974a06ca" contextRef="c20220930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">990,149</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_fb2ce086644c437499ac32ea8b2ab24d" contextRef="c20220930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">950,100</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_7b5eb73a704b42f985034bdd93235dd2" contextRef="c20220930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23</div>
</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f7" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f8"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e843" continuedAt="Text_791c82d809f0483a925020bb5ee57e844">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f8" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f9"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e844" continuedAt="Text_791c82d809f0483a925020bb5ee57e845">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 8pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2021</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (3)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_a02ee28d048e4f4a86d13e676be48142" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">120,868</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_2c0dd2ce365841a7940c2b161ab7aa5b" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_276eb2ce23b74c76b7109fee3b729859" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">120,868</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_e9495bbff93745cdbd73aaf148a9dd4a" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (3)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_92f2c745baa2467ebc8da9f308582732" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">182,634</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_4f65ddc8bb1f41b18f4a4fafb05aa5bf" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">182,634</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_cad6d847f28b41d1ba345ee379c53c3a" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_a2deb395404a40e59f04a7af68529744" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (5)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_8ac6126992144e2d902abafe0f05aaf1" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">174,464</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_c4b11390dafb4d68ab357a12be102e2b" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_984ae9d0003e4112b370b64ac08e73fa" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">174,464</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_0602b31c9430474ba3e3239fa80848d7" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (3)</div></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_a7b2fd7148674fabb6e271a364c858e7" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_c8b9f38165344705abd9b0e226858603" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,330</ix:nonFraction></div></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_309c74f6dec14486a89fc6b78983b26a" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">727,708</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_11ff54c661534a3abddbec83ad68c19a" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,065,490</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_d6e03911cdb74cbaa033e42a7ae570af" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,330</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f9" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f10"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e845" continuedAt="Text_791c82d809f0483a925020bb5ee57e846">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f10" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f11"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e846" continuedAt="Text_791c82d809f0483a925020bb5ee57e847">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following footnotes reference lines in our condensed consolidated balance sheet:</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f11" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f12"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e847" continuedAt="Text_791c82d809f0483a925020bb5ee57e848">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f12" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f13"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e848" continuedAt="Text_791c82d809f0483a925020bb5ee57e849">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_a07f61350d6c43dcbc95f9a5735b974a" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in cash and cash equivalents in our condensed consolidated balance sheet.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f13" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f14"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e849" continuedAt="Text_791c82d809f0483a925020bb5ee57e8410">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f14" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f15"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e8410" continuedAt="Text_791c82d809f0483a925020bb5ee57e8411">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_bd378771d36d4c53928130eb23540740" contextRef="c20220930_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">23.5</ix:nonFraction> million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f15" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f16"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e8411" continuedAt="Text_791c82d809f0483a925020bb5ee57e8412">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f16" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f17"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e8412" continuedAt="Text_791c82d809f0483a925020bb5ee57e8413">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_2009e9e101cd4940acd892bb1ca9a15f" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in short-term investments.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f17" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f18"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e8413" continuedAt="Text_791c82d809f0483a925020bb5ee57e8414">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f18" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f19"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e8414" continuedAt="Text_791c82d809f0483a925020bb5ee57e8415">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>
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  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f19" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f20"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e8415" continuedAt="Text_791c82d809f0483a925020bb5ee57e8416">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f20" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f21"><ix:continuation id="Text_791c82d809f0483a925020bb5ee57e8416">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>
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  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f21" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f22">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_ee2fc4b70a8245da91eab326d2d3097f22" continuedAt="Text_ee2fc4b70a8245da91eab326d2d3097f23">
<div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Convertible Notes</div>
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<div><br /></div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dfc304a4577d4a8b8ccf97e7be8f9791" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b605dc05faaa4ecf92f3388ccd8e6140" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes had a fair value of $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_886896b6a5b643a387fb328dcc366ca9" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">498.7</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_e2d5869342504cbea6cdb10162937afd" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">631.8</ix:nonFraction> million at September 30, 2022, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.</div>
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<div style="text-align: left; text-indent: -45pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#160; Income Taxes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2022, the Tax Cuts and Jobs Act of 2017, or TCJA, requires taxpayers to amortize research and development expenditures over <ix:nonNumeric name="ions:AmortizationPeriodForResearchAndDevelopmentExpenditures" id="Fact_763c8c79a6914eb6ab4fe0ff423711ca" contextRef="c20220101to20220930" format="ixt-sec:durwordsen">five years</ix:nonNumeric> pursuant to Internal Revenue Code, or IRC, Section 174. Although the U.S. Congress is considering legislation that would defer the amortization requirement to later years, we have no assurance that the provision will be repealed or otherwise modified. Since we expect taxable income in 2022, we recorded income tax expense of $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_a121ece11a5143edb5db059c6a48584e" contextRef="c20220701to20220930" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.3</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_6970ebf98cf0410b96e67074aa95aa1d" contextRef="c20220101to20220930" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.6</ix:nonFraction> million for the three months and nine months ended September 30, 2022, respectively, compared to income tax benefit of $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_3020d51b142e4dd0ba7b47c269b8aa0c" contextRef="c20210701to20210930" unitRef="U002" decimals="-5" scale="6" sign="-" format="ixt:num-dot-decimal">1.3</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_b6caed802528436294c3c7945fb6224d" contextRef="c20210101to20210930" unitRef="U002" decimals="-5" scale="6" sign="-" format="ixt:num-dot-decimal">0.9</ix:nonFraction> million for the same periods in 2021.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6.&#160; Collaborative Arrangements and Licensing Agreements</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Below, we have included our Biogen, Roche and Bayer collaborations, which are our only collaborations with substantive changes during </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2022</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, 2021</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Strategic Partnership</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Biogen</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#8217;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. We and Biogen are currently developing numerous investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, SMA, Angelman Syndrome, Alzheimer&#8217;s disease<sub>&#xA0;</sub>and Parkinson&#8217;s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through September 30, 2022, we have received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_4de0101278b94f98a15dfb2c4990f91e" contextRef="c20220930_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-8" scale="9" format="ixt:num-dot-decimal">3.4</ix:nonFraction> billion from our Biogen collaborations.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our condensed consolidated balance sheet at September 30, 2022 and December 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>included deferred revenue of $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_5178e097d0c342cf84072f17ad124e39" contextRef="c20220930_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">360.2</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_7b83a105f51e48c19c4fa834b14d4660" contextRef="c20211231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">407.5</ix:nonFraction> million, respectively, related to our relationship with Biogen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2022, we earned $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ab91654b7168476fa5495fb1d76b719d" contextRef="c20220701to20220930_TypeOfArrangementAxis_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">13</ix:nonFraction> million in milestone payments from Biogen when Biogen advanced <ix:nonFraction name="ions:NumberOfTargetsAdvanced" id="Fact_92927dcd49a748aa867e72d5b5af4971" contextRef="c20220701to20220930_TypeOfArrangementAxis_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> targets under our neurology collaborations. We recognized <ix:nonFraction name="ions:NumberOfMilestonePaymentsRecognizedInFull" id="Fact_60bf024f5d444594a6134a63e68ddcf6" contextRef="c20220701to20220930_TypeOfArrangementAxis_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember" unitRef="U016" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> of these milestone payments in full in the third quarter of 2022 because we did not have any remaining performance obligations related to the milestone payment. We added the other payment to the transaction price and allocated it to our R&amp;D services performance obligation for the 2012 neurology collaboration. We are recognizing revenue for our R&amp;D services performance obligation over our estimated period of performance. We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPotentialPayment" id="Fact_62248cc9a7314f0bb9f956f9d0ac4210" contextRef="c20220930_RangeAxis_MaximumMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">10</ix:nonFraction> million if Biogen advances another medicine under our 2013 strategic neurology collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Roche</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have <ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_38f0577e888645cca74688c25179fca8" contextRef="c20220930_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> collaborations with Roche, <ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_33bde39756ca4379bd2dd310a02ee4cf" contextRef="c20220930_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> to develop <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-FB-L</span><sub>Rx</sub> for the treatment of complement-mediated diseases, and <ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_657eab75b9474437934df84d901a4ec8" contextRef="c20220930_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> to <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">develop </span>treatments for Huntington's disease, or HD.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In October 2018, we entered into a collaboration agreement with Roche to develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We are currently conducting Phase 2 studies in </span><ix:nonFraction name="ions:NumberOfDiseaseIndications" id="Fact_45d405e1496f41f7b5c27b13bf1d876a" contextRef="c20220930_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U017" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> disease indications for IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span><ix:nonFraction name="ions:NumberOfDiseaseIndications" id="Fact_466db18ec812465e834221fd4f2e622c" contextRef="c20220930_ProductOrServiceAxis_GeographicAtrophyMember_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U017" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of patients with geographic atrophy, or GA, the advanced stage of dry AMD, and a </span><span style="-sec-ix-hidden:Fact_37bb84ab38b14330b8b82ce65b069cf8">second</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of patients with immunoglobulin A nephropathy, or IgAN. After positive data from a Phase 2 clinical study, Roche licensed IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in July 2022 for $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_98fd97d573804d9db350b06b2db5326c" contextRef="c20220701to20220930_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and </span>plans to advance <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-FB-L</span><sub>Rx</sub> into Phase 3 development for patients with IgAN<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. As a result, Roche is responsible for global development, regulatory and commercialization activities and costs for the Phase 3 IgAN study of IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We will continue to lead and conduct the open label Phase 2 study in patients with IgAN and the Phase 2 study in patients with GA</span>. In July 2022, we amended our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-FB-L</span><sub>Rx</sub> collaboration agreement with Roche. The amendment changed future potential milestone payments we could receive under the collaboration. We determined there were no changes that would require adjustments to revenue we previously recognized. Under our amended collaboration agreement, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" id="Fact_288407f2a20d4b1a8cda00b68b734242" contextRef="c20220930_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">145</ix:nonFraction> million in development milestones, $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" id="Fact_cb1b8e8b9a9d4381bd09ab4ae06d2f6f" contextRef="c20220930_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">279</ix:nonFraction> million in regulatory milestones and $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones" id="Fact_3e0c5fabff86437e9e95041edb079af8" contextRef="c20220930_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">280</ix:nonFraction> million in sales-related milestone payments. In addition, we are also eligible to receive tiered royalties from the high teens to <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_61411fb377434c5490912b77f454cdcf" contextRef="c20220101to20220930_RangeAxis_MaximumMember_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent on net sales.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the collaboration agreement with Roche to develop treatments for HD, we discovered and developed tominersen, an investigational medicine targeting huntingtin, or HTT, protein, through completion of our Phase 1/2 clinical study in people with early stage HD. In the fourth quarter of 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. Roche is responsible for all global development, regulatory and commercialization activities and costs for tominersen. In March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest HD based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded iDMC. In January 2022, Roche announced it is actively preparing to initiate a new Phase 2 study of tominersen in patients with HD. Post-hoc analyses from the GENERATION HD1 study suggested tominersen may benefit younger adult patients with lower disease burden. From inception through September 30, 2022, we have received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_e93d23b347974229a70b3880eddcfdd0" contextRef="c20220930_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">283</ix:nonFraction> million from our Roche collaborations.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2022 and 2021, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our condensed consolidated balance sheet at September 30, 2022 and December 31, 2021 included deferred revenue of $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_8981b91ed6f249dba1d77b44a687f85e" contextRef="c20220930_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">23.6</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_693ddcd6861c4a8bbdb099c85dab462b" contextRef="c20211231_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">31.6</ix:nonFraction> million, respectively, related to our relationship with Roche.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed above, in the third quarter of 2022, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_dc9cf764c46c4be5aa1f196f7244deac" contextRef="c20220701to20220930_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction> million payment from Roche when Roche licensed IONIS-FB-L<sub>Rx</sub>. We recognized the license fee as revenue in the third quarter of 2022 because Roche had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Roche. We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPotentialMilestonePayment" id="Fact_06384301f1d04442b3a1d04e44ae57e2" contextRef="c20220930_RangeAxis_MaximumMember_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">90</ix:nonFraction> million if Roche advances a medicine under our IONIS-FB-L<sub>Rx</sub> collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Bayer</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI<sub>Rx</sub> for the prevention of thrombosis. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI<sub>Rx</sub>, initiate development of fesomersen, an investigational LIgand-Conjugated Antisense medicine we designed to inhibit the production of Factor XI, and license fesomersen to Bayer. In the fourth quarter of 2022, Bayer communicated to us that it will discontinue the clinical development program for fesomersen and return fesomersen to us. We have received over $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_d026827cfb694dc6bb168adcf1f0cec2" contextRef="c20220930_TypeOfArrangementAxis_BayerCollaborationIonisFxiMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">190</ix:nonFraction> million from Bayer over the term of this collaboration.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7. Convertible Debt</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6084a279781c4f6f9d255000ab9021c3" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction> Percent</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Convertible Senior Notes and Call Spread</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we completed a $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_31b7ba9c70ea47c98e3db30445a91628" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">632.5</ix:nonFraction> million offering of convertible senior notes. We used a portion of the net proceeds from the issuance of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9dafbe4ac36f4acab7c5417e2b16fdb9" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes to repurchase $<ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_367cca58a7ca4ff88703902e4e0bd9d7" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">247.9</ix:nonFraction> million in principal of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_daaf05b5284740438b6e8f119ed98382" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes for $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_b88be17da074442d8e0174eda1c066ff" contextRef="c20210401to20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">257.0</ix:nonFraction> million.</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At September 30, 2022, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_851b6e16263b47a8a5a3b794b32dee59" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes outstanding (amounts in millions except interest rate and price per share data):</div>
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  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde">April 2026</span></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dce4bbae7b2a40908908ca4da1034984" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction> percent</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_b9aacb5cbdd246a29518869cf1580bba" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">76.39</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleSharesSubjectToConversion" id="Fact_36af5452ef2d4158ba6f36e437b52979" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a1c65db2db5e45bf9144abb23a3708cd" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes by increasing the effective conversion price on our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_47594a78eeb74261b797d8f322986fa4" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. We increased our effective conversion price to $<ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_adfab887b13140eda35dd28df11ca681" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">76.39</ix:nonFraction> with the same number of underlying shares as our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1e893f3eccd04fa886b5729d9095bb3a" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. The call spread cost us $<ix:nonFraction name="ions:CallSpread" id="Fact_9cea2f5d760e42c0a7580446a66d3538" contextRef="c20210401to20210430" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">46.9</ix:nonFraction> million, of which $<ix:nonFraction name="us-gaap:PaymentsForHedgeFinancingActivities" id="Fact_36a469c4005348aa8141ff489585a08c" contextRef="c20210401to20210430" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">136.7</ix:nonFraction> million was for the note hedge purchase, offset by $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfWarrants" id="Fact_9dc32db714544a28860e525c4fab30e8" contextRef="c20210401to20210430" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">89.8</ix:nonFraction> million we received for selling the warrants. Similar to our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_327d187d871445adb18503b7c83d8bb1" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1bb651c30fc64b0db83da188f8aae2f8" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. The note hedges will expire upon maturity of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ca5f6c96b1124b2989fd762efdf51a1e" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes, or April 2026. The note hedges and warrants are separate transactions and are not part of the terms of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_01da5b0bd9a8481f8816fdd4ee0aa0c5" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. The holders of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7c0a89b92f644ec1a10cc74660014eab" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes do not have any rights with respect to the note hedges and warrants.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our condensed consolidated balance sheet. See our Call Spread accounting policy in Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, in the Notes to the Condensed Consolidated Financial Statements. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_76ff515a60454ce18e1a9984840953ae" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction> Percent Convertible Senior Notes and Call Spread</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At September 30, 2022, we had the following <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e999f0a79cc5454dbb35d79507c6bf14" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):</div>
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<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_5b30f304e836422cb321c0bd36da9cea" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">548.8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec">December 2024</span></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_a9ed75c8530a4cdd980eb1dc32b37ca0" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.5</ix:nonFraction> percent</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_6424592d0e3847f9b21c7950d9891db7" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">83.28</ix:nonFraction></div></td>
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    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_257883a038234987a42360f37188d9b5" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">123.38</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleSharesSubjectToConversion" id="Fact_ed9c5d233d3b47b992cb88b28e7d96fe" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.6</ix:nonFraction></div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In conjunction with the issuance of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fce48022202d43bb90824a8ab622ba1e" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes in December 2019, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_74c63dcb37a94b7c96fcda23934eccde" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes by increasing the effective conversion price on our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5e16fd8ed7c44c38864b21191b33ad87" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We increased our effective conversion price to $</span><ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_706c33f17c1047e2b303834e2dfa9903" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">123.38</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> with the same number of underlying shares as our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8ada2275fc3149ba9239349b360d3ff0" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes. The call spread cost us $</span><ix:nonFraction name="ions:CallSpread" id="Fact_376edf8306554bc9be15b3e5059f9689" contextRef="c20191201to20191231" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">52.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, of which $</span><ix:nonFraction name="us-gaap:PaymentsForHedgeFinancingActivities" id="Fact_63109fd55a644feaa1ceeef8ebde9e37" contextRef="c20191201to20191231" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">108.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million was for the note hedge purchase, offset by $</span><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfWarrants" id="Fact_821561db37bf489ea047c585d83d7fb2" contextRef="c20191201to20191231" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">56.1</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we received for selling the warrants. Similar to our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8508261275f046e4bd44878636855c30" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a599520206b24338ba155a460138e93b" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The note hedges will expire upon maturity of the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9d674b898cb1469d9b4c18232244d3d9" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dcf07dd5cb7a40b58bbb604e293f91c3" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The holders of the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_cf200a768fcb4dcb9dda4aaad67a8130" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> do not have any rights with respect to the note hedges and warrants.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our condensed consolidated balance sheet. See our Call Spread accounting policy in Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, in the Notes to the Condensed Consolidated Financial Statements. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fd23717a1d4d4ec2ae3decc69589c581" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction> Percent Convertible Senior Notes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we repurchased $<ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_5733913e61d243aba64ac5cdde17967a" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">247.9</ix:nonFraction> million in aggregate principal amount of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7dce99cb33884aa695f60d9714cdbc63" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes in privately negotiated transactions. As a result of the repurchase, we recognized an $<ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_475d555508dd44ec879d8264ff4f449f" contextRef="c20210401to20210630_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.6</ix:nonFraction> million loss on early retirement of debt in the second quarter of 2021, reflecting the early retirement of a significant portion of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c7210172079a44a29a43562f67ccf9c3" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes. The loss on the early retirement of our debt is the difference between the amount paid to retire our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a41d730fa97348cbb6f1560579771061" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes and the net carrying balance of the liability at the time that we retired the debt. We paid the remaining principal balance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8adfad97b59c4a87a1edd27ef3c688bb" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes with $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_d0bfa204bf4c4321b5a5e9fcfe7261c1" contextRef="c20211101to20211130_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">62.0</ix:nonFraction> million of cash at maturity in November 2021.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Other Terms of Convertible Senior Notes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b2fc1c75f5c641f2b66eff5bf9e11829" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c98e7aaf45cf42a78ac646beebca0a17" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to </span><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_537b73ba3c5546d3ac7077aac87f42f6" contextRef="c20220101to20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_34a97d073e54403cb2f896dd5cda4e81" contextRef="c20220101to20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction></ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.</span> The <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_be103130a6d84fa7b52179f2877f3f4e" contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes were subject to similar terms.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8. Legal Proceedings</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On </span>August 5, 2021,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span><ix:nonFraction name="us-gaap:LossContingencyNumberOfPlaintiffs" id="Fact_503b427b9ee645449d3126e90259e66c" contextRef="c20210805to20210805_LitigationCaseAxis_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" unitRef="U018" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> purported former stockholders of Akcea filed an action in the Delaware Court of Chancery captioned John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al., C.A. </span>No<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>2021-0681<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or the Delaware Action. The plaintiffs in the Delaware Action asserted claims against (i) former members of Akcea&#8217;s board of directors; and (ii) Ionis, or collectively, the Defendants. The plaintiffs asserted putatively direct claims on behalf of a purported class of former Akcea stockholders. The plaintiffs in the Delaware Action asserted that the Defendants breached their fiduciary duties in connection with the </span>October 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> take-private transaction that Ionis and Akcea entered into, in which Akcea became a wholly-owned subsidiary of Ionis. We believe this lawsuit is without merit. However, the outcome of this lawsuit or any other lawsuit that may be filed challenging the </span>October 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> take-private transaction is uncertain. Accordingly, on </span>June 3, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the parties reached an agreement in principle to settle the Delaware Action for $</span><ix:nonFraction name="us-gaap:LitigationSettlementAmountAwardedToOtherParty" id="Fact_ae181b6dc4e7480babd58d0c1b90df5e" contextRef="c20220603to20220603_LitigationCaseAxis_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">12.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. A Stipulation and Agreement of Compromise, Settlement and Release, or the Stipulation and Settlement Agreement reflecting the terms of the proposed settlement was executed and filed with the Delaware Court of Chancery on </span>July 5, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. On </span>October 11, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the Delaware Court of Chancery entered an Order and Final Judgment, or the Order, approving the Stipulation and Settlement Agreement in full after determining that the Stipulation and Settlement Agreement was fair, reasonable, and adequate. The Order provides for the full settlement, satisfaction, compromise and release of all claims that were asserted in the Delaware Action. The Order contains </span>no<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> admission of wrongdoing on the part of any of the Defendants. We recorded a legal reserve of $</span><ix:nonFraction name="us-gaap:LitigationSettlementExpense" id="Fact_c1b4df7b7e2b4cbe9fa8f5accc6df72b" contextRef="c20220401to20220630_IncomeStatementLocationAxis_OtherNonoperatingIncomeExpenseMember_LitigationCaseAxis_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">12.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and the corresponding litigation settlement expense within other expense in the accompanying condensed consolidated statements of operations in the </span>second<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span>2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the proposed litigation settlement. In </span>the third quarter of 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we received insurance contributions toward the settlement in the amount of $</span><ix:nonFraction name="us-gaap:LossContingencyRelatedReceivableCarryingValueAdditions" id="Fact_48c7c37592344c0bac3b8f136a410292" contextRef="c20220701to20220930_LitigationCaseAxis_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" unitRef="U002" decimals="-5" scale="6">4.8</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million from our insurance carriers. We recorded the insurance contributions as a reduction to the litigation settlement expense in the </span>third<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span>2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On </span>January 19, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, a purported stockholder of Ionis filed a stockholder derivative complaint in the Delaware Court of Chancery captioned Leo Shumacher, et al. v. Joseph Loscalzo, et al., C.A. </span>No<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>2022-0059<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or the Shumacher Action. The complaint names Ionis' board of directors, or the Board, as defendants and names Ionis as a nominal defendant. The Shumacher Action Plaintiff asserts a breach of fiduciary duty claim against the Board for awarding and receiving allegedly excessive compensation. The Shumacher Action Plaintiff also asserts an unjust enrichment claim against the non-executive directors as a result of the compensation they received. The complaint seeks, among other things, damages, restitution, attorneys&#8217; fees and costs, and such other relief as deemed just and proper by the court. On </span>March 18, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we and the Board moved to dismiss the complaint. On </span>May 24, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the parties entered into a Stipulation and Agreement of Compromise, Settlement and Release.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On </span>May 25, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, another purported stockholder of Ionis filed a stockholder derivative complaint also in the Delaware Court of Chancery captioned Robert S. Cohen, et al. v. Joseph Loscalzo, et al., C.A. </span>No<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>2022-0453<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or the Cohen Action. The complaint names the Board as defendants and names Ionis as a nominal defendant. The Cohen Action Plaintiff asserts claims for breach of fiduciary duty, unjust enrichment, aiding and abetting breaches of fiduciary duty, and waste against the Board for awarding and receiving allegedly excessive non-executive director compensation for the years </span>2018, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, and </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. On </span>June 2, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the Cohen Action Plaintiff filed a motion to consolidate the related Cohen Action and Shumacher Action. On </span>July 5, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the Court denied the motion to consolidate in favor of the settlement pending in the Shumacher Action.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On July 18, 2022, we filed a Form 8-K disclosing the pending settlement and attaching the Notice of Pendency of Settlement of Action. On September 21, 2022, the Court held a hearing to consider whether the terms of the settlement should be approved, at which hearing the Cohen Action plaintiff objected to the settlement. At the conclusion of the hearing, the Court declined to approve the settlement and directed the parties to meet and confer on the issue of the scope of the release. We and our Board have denied, and continue to deny, any and all allegations of wrongdoing or liability asserted in the Shumacher and Cohen Actions.</div>
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<div style="text-align: left;"><a id="Item2MDAQ2Q3"><!--Anchor--></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 2.</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 72pt" class="TRGRRTFtoHTMLTab">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">MANAGEMENT&#8217;S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">In this Report on Form 10-Q, unless the context requires otherwise, &#8220;Ionis,&#8221; &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us,&#8221; means Ionis Pharmaceuticals, Inc. and its wholly owned subsidiary, Akcea Therapeutics, Inc.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Forward-Looking Statements</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">In addition to historical information contained in this Report on Form 10-Q, the Report includes forward-looking statements regarding our business and the therapeutic and commercial potential of SPINRAZA (nusinersen), TEGSEDI (inotersen), WAYLIVRA (volanesorsen), eplontersen, olezarsen, donidalorsen, ION363, pelacarsen, tofersen and our technologies and products in development. Any statement describing our goals, expectations, financial or other projections, intentions or beliefs, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Our forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those discussed in this report and described in additional detail in our annual report on Form 10-K for the year ended December 31, 2021, which is on file with the U.S. Securities and Exchange Commission and is available from us, and those identified within Part II Item 1A. Risk Factors of this Report. Although our forward-looking statements reflect the good faith judgment of our management, these statements are based only on facts and factors currently known by us. As a result, you are cautioned not to rely on these forward-looking statements.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="OverviewQ2Q3"><!--Anchor--></a>Overview</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are a leader in RNA-targeted therapeutics. We believe our medicines have the potential to pioneer new markets, change standards of care and transform the lives of people with devastating diseases. We currently have three marketed medicines- SPINRAZA, TEGSEDI and WAYLIVRA. We also have a rich late- and mid-stage pipeline primarily focused on our leading cardiovascular and neurology franchises. We currently have six medicines in Phase 3 development for eight indications. Recently, we reported positive Phase 3 interim analysis data from the NEURO-TTRansform study of eplontersen in patients with polyneuropathy caused by hereditary transthyretin amyloidosis, or ATTRv-PN. As a result, we plan to file a New Drug Application, or NDA, with the U.S. Food and Drug Administration, or FDA, by the end of 2022. Additionally, the FDA recently accepted Biogen&#8217;s NDA filing of tofersen for the treatment of superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS, and granted tofersen priority review. Tofersen&#8217;s Prescription Drug User Fee Act, or PDUFA, date is April 25, 2023. These achievements put us on track to potentially add two new marketed products to our commercial portfolio, if these medicines are approved. In addition, based on recent positive data from the Phase 2b study of bepirovirsen in patients with chronic hepatitis B virus, or HBV, and the Phase 2 study of IONIS-FB-L<sub>Rx</sub> in patients with immunoglobulin A nephropathy, or IgAN, our partners plan to advance these medicines into Phase 3 development, which would expand our late-stage pipeline to eight medicines in Phase 3 development for ten indications.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our multiple sources of revenue and strong balance sheet enable us to invest in our strategic priorities to build our commercial pipeline, expand and diversify our technology and deliver new medicines to the market. By continuing to focus on these priorities, we believe we are well positioned to drive future growth and to deliver increasing value for patients and shareholders.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Marketed Medicines</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA is the global market leader for the treatment of patients of all ages with spinal muscular atrophy, or SMA, a progressive, debilitating and often fatal genetic disease. Biogen is our partner responsible for commercializing SPINRAZA worldwide. From inception through September 30, 2022, we have earned more than $1.8 billion in revenues from our SPINRAZA collaboration, including more than $1.3 billion in royalties on sales of SPINRAZA.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI is a once weekly, self-administered subcutaneous medicine approved in the U.S., Europe, Canada and Brazil for the treatment of patients with polyneuropathy caused by ATTRv-PN. In 2021, we began selling TEGSEDI in Europe through our distribution agreement with Swedish Orphan Biovitrum AB, or Sobi. Additionally, in the second quarter of 2021, Sobi began distributing TEGSEDI in the U.S. and Canada. In Latin America, PTC Therapeutics International Limited, or PTC, is commercializing TEGSEDI beginning with Brazil.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAYLIVRA is a once weekly, self-administered, subcutaneous medicine indicated as an adjunct to diet in adult patients with genetically confirmed familial chylomicronemia syndrome, or FCS, and at high risk for pancreatitis. In 2021, we began selling WAYLIVRA in Europe through our distribution agreement with Sobi. Under our exclusive license agreement with PTC, PTC is working to provide access to WAYLIVRA across Latin America, beginning in Brazil. In the third quarter of 2021, the National Health Surveillance Agency (Ag&#234;ncia Nacional de Vigil&#226;ncia Sanit&#225;ria), or ANVISA, approved WAYLIVRA in Brazil. In December 2021, PTC submitted an application to ANVISA for approval of WAYLIVRA for the treatment of familial partial lipodystrophy, or FPL, in Brazil. If approved, Waylivra will be the first approved treatment for patients with FPL in Brazil.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi, we retained the marketing authorizations for TEGSEDI and WAYLIVRA in major markets. We continue to supply commercial product to Sobi and manage regulatory and manufacturing processes, as well as relationships with key opinion leaders. We also continue to lead the TEGSEDI and WAYLIVRA global commercial strategy. In connection with the agreements, we restructured our European operations in the first quarter of 2021, and we restructured our North American TEGSEDI operations in the second quarter of 2021.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Medicines in Phase 3 Studies</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We currently have six medicines in Phase 3 studies for eight indications, which include:</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen: our medicine in development for transthyretin amyloidosis, or ATTR</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are currently conducting the Phase 3 NEURO-TTransform study in patients with ATTRv-PN, the Phase 3 CARDIO-TTransform study in patients with ATTR cardiomyopathy, or ATTR-CM, and additional studies supporting our ATTR development program</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2022, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e presented positive results from an interim analysis of the Phase 3 NEURO-TTRansform study of eplontersen in patients with ATTRv-PN at the International Symposium on Amyloidosis</span></div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2022, we expanded enrollment in the Phase 3 CARDIO-TTRansform study of eplontersen in patients with ATTR cardiomyopathy, or ATTR-CM</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen was granted orphan drug designation by the FDA for the treatment of patients with ATTR</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tofersen: our medicine in development for SOD1-ALS</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen is developing tofersen for the treatment of SOD-1 ALS, including conducting the ongoing Phase 3 VALOR open label extension, or OLE, study in patients with SOD1-ALS and the ongoing Phase 3 ATLAS study in presymptomatic SOD-1 patients</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tofersen is currently under priority review with the FDA and has a PDUFA action date of April 25, 2023</div></td>
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<div><a id="_Hlk117845312"><!--Anchor--></a></div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In June 2022, Biogen presented new data from the ongoing VALOR OLE study at the European Network to Cure ALS meeting. These data were included in the NDA filing</span></div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Olezarsen: our medicine in development for FCS and severe hypertriglyceridemia, or SHTG</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are currently conducting a broad development program for olezarsen that includes the BALANCE study in patients with FCS and three Phase 3 studies supporting development for the treatment of SHTG, CORE, CORE2 and ESSENCE</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2022, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e achieved full enrollment in the BALANCE Phase 3 study in patients with FCS supporting data readout mid-year 2023</span></div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2022, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e initiated CORE2, a confirmatory Phase 3 study of olezarsen in patients with SHTG</span></div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2022, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e initiated ESSENCE, a supporting Phase 3 study of olezarsen in patients with SHTG or hypertriglyceridemia and atherosclerotic cardiovascular disease</span></div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pelacarsen: our medicine in development for lipoprotein(a), or Lp(a), driven cardiovascular disease</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">o</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis is developing pelacarsen, including conducting the ongoing Lp(a) HORIZON Phase 3 cardiovascular outcome study in patients with established cardiovascular disease and elevated Lp(a)</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2022, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Novartis achieved full enrollment in the Lp(a) HORIZON Phase 3 cardiovascular outcome study</span></div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Donidalorsen: our medicine in development for hereditary angioedema, or HAE</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">o</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are currently conducting the OASIS study in patients with HAE and OASIS Plus supportive study for HAE patients previously treated with other prophylactic therapies</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We plan to present new efficacy and safety results from the Phase 2 OLE study of donidalorsen in HAE patients treated for one year at the American College of Allergy, Asthma and Immunology Annual Scientific Meeting in November 2022</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ION363: our medicine in development for amyotrophic lateral sclerosis, or ALS, with mutations in the fused in sarcoma gene, or FUS. FUS-ALS is the most common cause of juvenile-onset ALS</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">o</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are currently conducting a Phase 3 study of ION363 in juvenile and adult patients with FUS-ALS and enrollment is ongoing</div></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Third Quarter 2022 and Recent Updates on Certain Mid-Stage Pipeline Medicines</div>
<div><br /></div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">GSK presented positive end of study data from the Phase 2b B-Clear study of bepirovirsen demonstrating potential for functional cures in patients with chronic hepatitis B; GSK plans to advance bepirovirsen into Phase 3 development in the first half of 2023</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We presented positive data from the Phase 2 study of IONIS-FB-L<sub>Rx</sub> in patients with IgAN; Roche plans to advance IONIS-FB-L<sub>Rx</sub> into Phase 3 development in the first half of 2023</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Bayer presented positive data from the Phase 2b study of fesomersen in patients with end-stage renal disease; we regained rights to fesomersen from Bayer and are assessing next steps</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Roche presented the Phase 2 GENERATION HD2 study design of tominersen in Huntington&#8217;s disease, or HD, patients; Roche plans to begin enrollment in early 2023</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reported ION449 (AZD8233) targeting PCSK9 met the primary endpoint in Phase 2b SOLANO study in patients with hypercholesterolemia; based on pre-specified efficacy criteria, AstraZeneca is not advancing ION449</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">COVID-19</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As a company focused on improving the health of people around the world, our priority during the COVID-19 pandemic is the safety of our employees, their families, the healthcare workers who work with us and the patients who rely on our medicines. We are also focused on maintaining the quality of our studies and minimizing the impact to timelines. While the COVID-19 pandemic has impacted some areas of our business, we believe our mitigation efforts and financial strength will enable us to continue to manage through the pandemic and execute on our strategic initiatives. Because the situation is extremely fluid, we are continuing to monitor the impact COVID-19 could have on our business, including the impact on our commercial products and the medicines in our pipeline.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Financial Highlights</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our financial results (in millions):</div>
<div><br /></div>
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    <td valign="bottom" style="vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">159.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">133.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">435.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">370.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
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    <td valign="bottom" style="vertical-align: top; width: 52%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">218.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">218.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">637.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">621.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss from operations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(59.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(85.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(202.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(250.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(47.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(82.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(217.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(253.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>
<div><br /></div>
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  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue increased 20 percent for the third quarter of 2022 and 18 percent on a year-to-date basis compared to the same periods in 2021 driven by significant partner payments earned across multiple programs</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses were flat for the three months ended September 30, 2022 compared to the same period in 2021 and increased 3 percent for the nine months ended September 30, 2022. Refer to the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Results of Operations</span> section for discussions on period-over-period changes for the various components of operating expenses</div></td>
  </tr>
</table>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of September 30, 2022, we had $2.0 billion in cash and short-term investments. Subsequent to September 30, 2022, we entered into several real-estate transactions, which increased our cash balance. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Refer to the section titled, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Liquidity and Capital Resources</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for further details on these real-estate transactions.</span></div></td>
  </tr>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Eplontersen Collaboration with AstraZeneca</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our financial results for the nine months ended September 30, 2022 reflected the cost-sharing provisions related to our eplontersen collaboration with AstraZeneca to develop and commercialize eplontersen for the treatment of ATTR. Under the terms of the collaboration agreement, AstraZeneca is paying 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we are recognizing as research and development, or R&amp;D, revenue the 55 percent of cost-share funding AstraZeneca is responsible for, net of our share of AstraZeneca&#8217;s development expenses, in the same period we incur the related development expenses. In the nine months ended September 30, 2022, we have earned $55 million in joint development revenue under this collaboration.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As AstraZeneca is responsible for the majority of the medical affairs and commercial costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we are recognizing cost-share funding we receive from AstraZeneca related to these activities as a reduction of our medical affairs and commercialization expenses, which we classify as R&amp;D and selling, general and administrative, or SG&amp;A, expenses, respectively. In the nine months ended September 30, 2022, we recognized $1.4 million and $1.5 million of medical affairs expenses and commercialization expenses for eplontersen, respectively, net of cost-share funding from AstraZeneca. We expect our medical affairs and commercialization expenses to increase as our collaboration with AstraZeneca progresses.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of the financial impacts on our statement of operations for the nine months ended September 30, 2022 of the joint development activities under our eplontersen collaboration with AstraZeneca:</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 20.27%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Collaboration Activities</div></td>
    <td style="width: 1.52%; vertical-align: bottom;">&#160;</td>
    <td style="width: 19.97%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Financial Statement Line</div></td>
    <td style="width: 2.07%; vertical-align: bottom;">&#160;</td>
    <td colspan="3" style="width: 56.17%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impact of Cost-Sharing Provisions on our Statement of Operations</div></td>
  </tr>
  <tr>
    <td rowspan="3" style="width: 20.27%; vertical-align: middle;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 Development:</div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis leads and conducts</div></td>
    <td style="width: 1.52%; vertical-align: middle;">&#160;</td>
    <td style="width: 19.97%; vertical-align: middle; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen Joint Development Revenue</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(R&amp;D Revenue)</div></td>
    <td style="width: 2.07%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 8.26%; vertical-align: middle; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$55M</div></td>
    <td style="width: 1.24%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 46.67%; vertical-align: middle; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55% of Ionis&#8217; Phase 3 development expenses, including internal+external costs &amp; CMC costs, net of our share of AstraZeneca&#8217;s Phase 3 development expenses</div></td>
  </tr>
  <tr>
    <td style="width: 1.52%; vertical-align: middle;">&#160;</td>
    <td style="width: 19.97%; vertical-align: middle;">&#160;</td>
    <td style="width: 2.07%; vertical-align: middle;">&#160;</td>
    <td style="width: 8.26%; vertical-align: middle;">&#160;</td>
    <td style="width: 1.24%; vertical-align: middle;">&#160;</td>
    <td style="width: 46.67%; vertical-align: middle;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 1.52%; vertical-align: middle;">&#160;</td>
    <td style="width: 19.97%; vertical-align: middle; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Development Expenses (R&amp;D expenses)</div></td>
    <td style="width: 2.07%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 8.26%; vertical-align: middle; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$107M</div></td>
    <td style="width: 1.24%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 46.67%; vertical-align: middle; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100% of Ionis&#8217; Phase 3 development expenses</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Critical Accounting Estimates</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the U.S. As such, we make certain estimates, judgments and assumptions that we believe are reasonable, based upon the information available to us. These judgments involve making estimates about the effect of matters that are inherently uncertain and may significantly impact our quarterly or annual results of operations and financial condition. Each quarter, our senior management reviews the development, selection and disclosure of such estimates with the audit committee of our board of directors. The following are our significant accounting estimates, which we believe are the most critical to aid in fully understanding and evaluating our reported financial results:</div>
<div><br /></div>
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  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Assessing the propriety of revenue recognition and associated deferred revenue; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Determining the appropriate cost estimates for unbilled preclinical studies and clinical development activities.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">There have been no other material changes to our critical accounting policies and estimates from the information provided in Item 7, &#8220;Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations&#8221; included in our Annual Report on Form 10-K for the year ended</span>&#xA0;December 31, 2021.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="ResultsOfOperationsQ2Q3"><!--Anchor--></a>Results of Operations</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Total revenues for the three and </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> were $</span>159.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>435.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, respectively, compared to $</span>133.1<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>370.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the same periods in </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and were comprised of the following (amounts in millions):</span></div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46.9</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.5</div></td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">84.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">222.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">255.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">License fees</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other services</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.2</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaborative agreement revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">157.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">115.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen joint development revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">87.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">212.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">115.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 81pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">159.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">133.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">435.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">370.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
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<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our revenue for the three and nine months ended September 30, 2022 increased 20 percent and 18 percent compared to the same periods in 2021, respectively. </span>The increase was driven by significant partner payments we earned across multiple partnered programs, including <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$85 million from Biogen for advancing several neurology disease programs,</span> $63 million from Roche for advancing and licensing IONIS-FB-L<sub>Rx</sub> and $55 million from AstraZeneca for its share of the global Phase 3 development costs for eplontersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our commercial revenue for the three and nine months ended September 30, 2022 decreased 15 percent and 13 percent compared to the same periods in 2021, respectively. SPINRAZA royalties for the three and nine months ended September 30, 2022 decreased 7 percent and 12 percent compared to the same periods in 2021, respectively. In the U.S., SPINRAZA sales were flat in the first nine months of 2022 compared to the same period in 2021</span>. Outside of the U.S., SPINRAZA royalties decreased in the first nine months of 2022 compared to the same period in 2021 due to lower SPINRAZA product sales primarily due to decreased pricing, foreign currency exchange and competition. TEGSEDI and WAYLIVRA revenue decreased primarily due to the shift to distribution fees in 2021.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Operating Expenses</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operating expenses were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">195.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">185.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">563.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">498.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">195.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">188.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">563.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">522.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">98.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">218.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">218.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">637.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">621.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operating expenses, excluding non-cash compensation expense related to equity awards, increased for the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">three and nine months ended September 30, 2022 </span>compared to the same periods in 2021. For both periods, our R&amp;D expenses increased due to our investments in advancing our late-stage pipeline, including our expanding number of Phase 3 studies, which doubled over the course of 2021 from three to six studies. Our SG&amp;A expenses increased for the three months ended September 30, 2022 compared to the same period in 2021 due to our go-to-market activities for eplontersen, donidalorsen and olezarsen. Our SG&amp;A expenses decreased for the nine months ended September 30, 2022 compared to the same period in 2021 as a result of savings we realized from integrating Akcea and restructuring our commercial operations for TEGSEDI and WAYLIVRA, partially offset by the increase in expenses related to our go-to-market activities in the third quarter of 2022. We expect our operating expenses, excluding non-cash compensation expense related to equity awards, to increase during the fourth quarter of 2022 compared to the same period in 2021 as we continue to advance our late- and mid-stage pipeline, invest in expanding and diversifying our technology and advance our go-to-market activities<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our non-cash compensation expense related to equity awards decreased in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">three and nine months ended September 30, 2022 </span>compared to the same periods in 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> due to decreased headcount of longer-tenured employees as a result of restructuring our commercial operations for TEGSEDI and WAYLIVRA.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To analyze and compare our results of operations to other similar companies, we believe it is important to exclude non-cash compensation expense related to equity awards from our operating expenses. We believe non-cash compensation expense related to equity awards is not indicative of our operating results or cash flows from our operations. Further, we internally evaluate the performance of our operations excluding it.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Cost of Sales</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales is comprised of costs related to our commercial revenue, which consisted of manufacturing costs, including certain fixed costs, transportation and freight, indirect overhead costs associated with the manufacturing and distribution of TEGSEDI and WAYLIVRA and certain associated period costs.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total cost of sales</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Research, Development and Patent Expenses</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and patent expenses consist of expenses for antisense drug discovery, antisense drug development, manufacturing and development chemistry and R&amp;D support expenses.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on research, development and patent expenses (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">165.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">159.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">469.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">383.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research, development and patent expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">165.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">161.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">469.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">391.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research, development and patent expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">183.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">184.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">524.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">463.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
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<div class="BRPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34</div>
</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Antisense Drug Discovery</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use our proprietary antisense technology to generate information about the function of genes and to determine the value of genes as drug discovery targets. We use this information to direct our own antisense drug discovery research, and that of our partners. Antisense drug discovery is also the function that is responsible for advancing our antisense core technology. This function is also responsible for making investments in complementary technologies to expand the reach of antisense technology.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our antisense drug discovery expenses were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total antisense drug discovery expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">123.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense drug discovery expenses, excluding non-cash compensation expense related to equity awards, decreased in the three and nine months ended September 30, 2022 compared to the same periods in 2021. In the first nine months of 2021, we incurred certain non-recurring licensing expenses, including $35 million for licensing Bicycle Therapeutics&#8217; peptide technology. These non-recurring licensing expenses resulted in higher antisense drug discovery expenses in the three and nine months ended September 30, 2021.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Antisense Drug Development</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth drug development expenses, including expenses for our marketed medicines and those in Phase 3 development for which we have incurred significant costs (in millions):</div>
<div><br /></div>
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    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Olezarsen</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">91.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total antisense drug development, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">108.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">80.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">294.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">210.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total antisense drug development expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">116.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">310.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">241.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our development expenses, excluding non-cash compensation expense related to equity awards, increased for the three and nine months ended September 30, 2022 compared to the same periods in 2021 primarily due to our advancing late-stage pipeline, including our expanding number of Phase 3 studies, which doubled over the course of 2021 from three to six studies. Non-cash compensation expense related to equity awards decreased in 2022 compared to 2021 due to reduced headcount of longer-tenured employees as a result of our restructured commercial operations.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may conduct multiple clinical trials on a drug candidate, including multiple clinical trials for the various indications we may be studying. Furthermore, as we obtain results from trials, we may elect to discontinue clinical trials for certain drug candidates in certain indications in order to focus our resources on more promising drug candidates or indications. Our Phase 1 and Phase 2 programs are clinical research programs that fuel our Phase 3 pipeline. When our medicines are in Phase 1 or Phase 2 clinical trials, they are in a dynamic state in which we may adjust the development strategy for each medicine. Although we may characterize a medicine as &#8220;in Phase 1&#8221; or &#8220;in Phase 2,&#8221; it does not mean that we are conducting a single, well-defined study with dedicated resources. Instead, we allocate our internal resources on a shared basis across numerous medicines based on each medicine&#8217;s particular needs at that time. This means we are constantly shifting resources among medicines. Therefore, what we spend on each medicine during a particular period is usually a function of what is required to keep the medicines progressing in clinical development, not what medicines we think are most important. For example, the number of people required to start a new study is large, the number of people required to keep a study going is modest and the number of people required to finish a study is large. However, such fluctuations are not indicative of a shift in our emphasis from one medicine to another and cannot be used to accurately predict future costs for each medicine. And, because we always have numerous medicines in preclinical and early stage clinical research, the fluctuations in expenses from medicine to medicine, in large part, offset one another. If we partner a medicine, it may affect the size of a trial, its timing, its total cost and the timing of the related costs.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Medical Affairs</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our medical affairs function is responsible for communicating scientific and clinical information to healthcare providers, medical professionals and patients.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our medical affairs expenses were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div> </div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Medical affairs expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total medical affairs expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We expect medical affairs expenses to continue increasing as we advance our late-stage pipeline.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Manufacturing and Development Chemistry</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenditures in our manufacturing and development chemistry function consist primarily of personnel costs, specialized chemicals for oligonucleotide manufacturing, laboratory supplies and outside services. Our manufacturing and development chemistry function is responsible for providing drug supplies to antisense drug development and our collaboration partners. Our manufacturing procedures include testing to satisfy good laboratory and good manufacturing practice requirements.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our manufacturing and development chemistry expenses were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Manufacturing and development chemistry expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total manufacturing and development chemistry expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total manufacturing and development chemistry expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Manufacturing and development chemistry expenses, excluding non-cash compensation expense related to equity awards, increased in the three and nine months ended September 30, 2022 compared to the same periods in 2021</span>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">due to increased costs we incurred in preparation for our near-term commercial launches, including manufacturing costs and activities for eplontersen, olezarsen and donidalorsen.</span></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">36</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">R&amp;D Support</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our research, development and patent expenses, we include support costs such as rent, repair and maintenance for buildings and equipment, utilities, depreciation of laboratory equipment and facilities, amortization of our intellectual property, informatics costs, procurement costs and waste disposal costs. We call these costs R&amp;D support expenses.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on R&amp;D support expenses (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Personnel costs</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Occupancy</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patent expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Insurance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.5</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D support expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D support expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">51.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
  </tr>
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<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D support expenses, excluding non-cash compensation expense related to equity awards, for the three and nine months ended September 30, 2022 increased compared to the same periods in 2021. The increase was primarily related to increased occupancy and personnel costs to support advancing our pipeline and our technology. In October 2022, we executed a sale and leaseback transaction for our headquarters in Carlsbad, California. As a result, our occupancy costs will increase beginning in the fourth quarter of 2022 because we will begin incurring rent expense for these facilities.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Selling, General and Administrative Expenses</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative, or SG&amp;A, expenses include personnel and outside costs associated with the pre-commercialization and commercialization activities for our medicines and costs to support our company, our employees and our stockholders including, legal, human resources, investor relations, and finance. Additionally, we include in selling, general and administrative expenses such costs as rent, repair and maintenance of buildings and equipment, depreciation and utilities costs that we need to support the corporate functions listed above. We also include fees we owe under our in-licensing agreements related to SPINRAZA.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on SG&amp;A expenses (in millions):</div>
<div><br /></div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">106.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total selling, general and administrative expenses, excluding non-cash compensation related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">122.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total selling, general and administrative expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">102.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">148.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SG&amp;A expenses, excluding non-cash compensation expense related to equity awards, increased for the three months ended September 30, 2022 compared to the same period in 2021 due to our go-to-market activities for eplontersen, donidalorsen and olezarsen.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> SG&amp;A expenses, excluding non-cash compensation expense related to equity awards, for the nine months ended September 30, 2022 decreased compared to the same period in 2021 due to operating efficiencies achieved from the Akcea Merger and restructuring our commercial operations for TEGSEDI and WAYLIVRA, partially offset by increased expenses for our go-to-market preparations for our near-term commercial opportunities. Non-cash compensation expense related to equity awards decreased in the three and nine months ended September 30, 2022 compared to the same periods in 2021 due to reduced headcount as a result of the Akcea Merger and our restructured commercial operations.</span></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Investment Income</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on investment income (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment income</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our investment income increased for the three and nine months ended&#xA0;September 30, 2022 due to higher interest rates in the nine months ended September 30, 2022 compared to the same period in 2021.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Interest Expense</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on interest expense (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash amortization of debt issuance costs</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense payable in cash</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest on mortgages for primary R&amp;D and manufacturing facilities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px;"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total interest expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Gain (Loss) on Investments</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on gain (loss) on investments (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gain (loss) on investments</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The period-over-period fluctuations in our gain (loss) on investments were primarily driven by changes in fair value of our investments in publicly held biotechnology companies.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Other Expense</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the second quarter of 2022, we recorded a non-operating expense of $12.5 million related to a settlement agreement for a litigation claim that we determined to be probable and estimable as of June 30, 2022. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the third quarter of 2022</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we received insurance contributions toward the settlement in the amount of $4.8 million from our insurance carriers. We recorded the insurance contributions as a reduction to the litigation settlement expense in the third quarter of 2022</span>. Refer to Note 8, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Legal Proceedings</span>, for further details regarding the litigation.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, as a result of a debt offering and debt repurchase, we recorded an $8.6 million loss on early retirement of debt, reflecting the early retirement of a portion of our 1% Notes, in the second quarter of 2022. The loss on the early retirement of our debt is the difference between the amount we paid to retire our 1% Notes and the net carrying balance of the liability at the time that we retired the debt.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Income Tax Expense</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2022, the Tax Cuts and Jobs Act of 2017, or TCJA, requires taxpayers to amortize research and development expenditures over five years pursuant to IRC Section 174. Although the U.S. Congress is considering legislation that would defer the amortization requirement to later years, we have no assurance that the provision will be repealed or otherwise modified. Since we expect taxable income in 2022, we recorded income tax expense of $0.3 million and $3.6 million for the three and nine months ended September 30, 2022, respectively, compared to income tax benefit of $1.3 million and $0.9 million for the same periods in 2021.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Net Loss<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and Net Loss per Share</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We had a net loss of $47.0 million and $217.3 million for the three and nine months ended&#xA0;September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively. </span>We had a net loss of $82.5 million and $253.2 million for the same periods in 2021. Our net loss decreased for the three and nine months ended September 30, 2022 compared to the same period in 2021 primarily due to increased revenue, partially offset by increased expenses year-over-year, as discussed in the revenue and expense sections, respectively. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Basic and diluted net loss per share for the three and </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> were $</span>0.33<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and $</span>1.53<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively, compared to $</span>0.58<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and $</span>1.80<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the same periods in </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="LiquidityQ2Q3"><!--Anchor--></a>Liquidity and Capital Resources</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have financed our operations primarily from research and development collaborative agreements. We also finance our operations from commercial revenue from SPINRAZA royalties and TEGSEDI and WAYLIVRA commercial revenue. From our inception through </span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have earned approximately</span> $6.3&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">billion in revenue. We have also financed our operations through the sale of our equity securities and the issuance of long-term debt. From the time we were founded through</span>&#xA0;September 30, 2022, we have raised net proceeds of approximately $2.0 billion from the sale of our equity securities. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additionally, from our inception through </span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have borrowed approximately</span> $2.1 billion under long-term debt arrangements to finance a portion of our operations.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cash, cash equivalents and short-term investments, debt obligations and working capital did not change significantly from December 31, 2021 to September 30, 2022.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our contractual obligations as of September 30, 2022. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The table provides a breakdown of when obligations become due. We provide a more detailed description of the major components of our debt in the paragraphs following the table:</span></div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contractual Obligations</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Payments Due by Period (in millions)</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(selected balances described below)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 1 year</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">More than 1 year</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0% Notes (principal payable)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 64%;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125% Notes (principal and interest payable)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">550.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">549.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building mortgage payments (principal and interest payable)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 64%;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating leases</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other obligations (principal and interest payable)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,280.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,272.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
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<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our contractual obligations consist primarily of our convertible debt. In addition, we also have facility mortgages, facility leases, equipment financing arrangements and other obligations. Due to the uncertainty with respect to the timing of future cash flows associated with our unrecognized tax benefits, we are unable to make reasonably reliable estimates of the period of cash settlement with the respective taxing authorities. Therefore, we have excluded our gross unrecognized tax benefits from our contractual obligations table above. We have not entered into, nor do we currently have, any off-balance sheet arrangements (as defined under SEC rules).</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we entered into a build-to-suit lease in which the lessor will construct a new development chemistry and manufacturing facility to support our continued our continued growth. In addition, we entered into a sale and leaseback agreement for our headquarters location in October 2022. The table above does not include the lease obligations related to these transactions or the extinguishment of the mortgage because they closed subsequent to September 30, 2022.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Convertible Debt and Call Spread</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Refer to our Convertible Debt and Call Spread accounting policies in Note 2, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, and Note 7, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Convertible Debt</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, in the Notes to our condensed consolidated financial statements for the significant terms of each convertible debt instrument.</span></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Operating Facilities</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2017, we purchased the building that houses our primary R&amp;D facility for $79.4 million and our manufacturing facility for $14.0 million. We financed the purchase of these two facilities with mortgage debt of $60.4 million in total. Our primary R&amp;D facility mortgage has an interest rate of 3.88 percent. Our manufacturing facility mortgage has an interest rate of 4.20 percent. During the first five years of both mortgages, we were only required to make interest payments. Both mortgages mature in August 2027.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we concurrently entered into two purchase and sale agreements with a real estate investor. Under the agreements, we sold and leased back the facilities at our headquarters location in Carlsbad, California and will sell, subject to meeting certain closing conditions, two lots of undeveloped land adjacent to our headquarters. We sold the facilities at our headquarters for a total purchase price of $263.4 million and we expect to receive total proceeds of $33.0 million upon the close of the sale of the two lots. We used a portion of the sale proceeds to extinguish our mortgage debt on our headquarters facilities of $51.3 million. The initial lease term for our headquarters facilities is 15 years with options to extend the lease for two additional terms of five years each. In connection with the sale of our two undeveloped lots, we will enter into a build-to-suit lease agreement with the same real estate investor who will build a new R&amp;D facility for us on those lots. Once this new facility is completed, our lease will commence.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility in Oceanside, California. The lessor will develop and construct a 217,000-square-foot building, composed of manufacturing space, office space, research and development space and warehouse space. We will design and construct tenant improvements to customize the facility&#8217;s interior space. We will lease the facility for an initial term of 20 years and 3 months with options to extend the lease for two additional terms of 10 years each. The lease will commence when the lessor's construction is complete and we are able to occupy the facility.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Other Obligations</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to contractual obligations, we had outstanding purchase orders as of September 30, 2022&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for the purchase of services, capital equipment and materials as part of our normal course of business.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may enter into additional collaborations with partners which could provide for additional revenue to us and we may incur additional cash expenditures related to our obligations under any of the new agreements we may enter into. We currently intend to use our cash, cash equivalents and short-term investments to finance our activities. However, we may also pursue other financing alternatives, like issuing additional shares of our common stock, issuing debt instruments, refinancing our existing debt, or securing lines of credit. Whether we use our existing capital resources or choose to obtain financing will depend on various factors, including the future success of our business, the prevailing interest rate environment and the condition of financial markets generally.</div>
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<div><a id="Item3MarketRisk"><!--Anchor--></a></div>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are exposed to changes in interest rates primarily from our investments in certain short-term investments. We primarily invest our excess cash in highly liquid short-term investments of the U.S. Treasury and reputable financial institutions, corporations, and U.S. government agencies with strong credit ratings. We typically hold our investments for the duration of the term of the respective instrument. We do not utilize derivative financial instruments, derivative commodity instruments or other market risk sensitive instruments, positions or transactions to manage exposure to interest rate changes. Accordingly, we believe that, while the securities we hold are subject to changes in the financial standing of the issuer of such securities, we are not subject to any material risks arising from changes in interest rates, foreign currency exchange rates, commodity prices, equity prices or other market changes that affect market risk sensitive instruments.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also exposed to changes in foreign currency exchange rates as we have foreign subsidiaries with functional currencies other than the U.S. dollar. We translate our subsidiaries&#8217; functional currencies into our reporting currency, the U.S. dollar. As a result, our financial position, results of operations and cash flows can be affected by market fluctuations in the foreign currencies to U.S. dollar exchange rate, which are difficult to predict. A hypothetical 10 percent change in foreign exchange rates during any of the periods presented would not have had a material impact on our condensed consolidated financial statements.</div>
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<div><a id="Item4Controls"><!--Anchor--></a></div>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONTROLS AND PROCEDURES</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We maintain disclosure controls and procedures that are designed to ensure that information we are required to disclose in our Exchange Act reports is recorded, processed, summarized and reported within the time periods specified in the SEC&#8217;s rules and forms, and that such information is accumulated and communicated to our management, including our Chief Executive Officer and Chief Financial Officer, as appropriate, to allow timely decisions regarding required disclosure. We design and evaluate our disclosure controls and procedures recognizing that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance and not absolute assurance of achieving the desired control objectives.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of our most recently completed fiscal year and as of the end of the period covered by this Quarterly Report on Form 10-Q, we carried out an evaluation of the effectiveness of the design and operation of our disclosure controls and procedures, as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended, under the supervision and with the participation of our management, including our Chief Executive Officer and Chief Financial Officer. Based on our evaluation, our Chief Executive Officer and Chief Financial Officer concluded that our disclosure controls and procedures were effective as of September 30, 2022. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">There have been no significant changes in our internal controls or in other factors that could significantly affect internal controls subsequent to</span>&#xA0;September 30, 2022.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also performed an evaluation of any changes in our internal controls over financial reporting that occurred during our last fiscal quarter and that have materially affected, or are reasonably likely to materially affect, our internal controls over financial reporting. We conducted this evaluation under the supervision of and with the participation of our management, including our Chief Executive Officer and Chief Financial Officer. That evaluation did not identify any changes in our internal controls over financial reporting that occurred during our latest fiscal quarter and that have materially affected, or are reasonably likely to materially affect, our internal controls over financial reporting.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="PARTII"><!--Anchor--></a>PART II &#8212; OTHER INFORMATION</div>
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<div><a id="ITEM1"><!--Anchor--></a></div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">LEGAL PROCEEDINGS</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On August 5, 2021, four purported former stockholders of Akcea filed an action in the Delaware Court of Chancery captioned John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al., C.A. No. 2021-0681, or the Delaware Action. The plaintiffs in the Delaware Action asserted claims against (i) former members of Akcea&#8217;s board of directors; and (ii) Ionis, or collectively, the Defendants. The plaintiffs asserted putatively direct claims on behalf of a purported class of former Akcea stockholders. The plaintiffs in the Delaware Action asserted that the Defendants breached their fiduciary duties in connection with the October 2020 take-private transaction that Ionis and Akcea entered into, in which Akcea became a wholly-owned subsidiary of Ionis.</span>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Ionis believes this lawsuit is without merit. However, the outcome of this lawsuit or any other lawsuit that may be filed challenging the October 2020 take-private transaction is uncertain. Accordingly, on June 3, 2022, the parties reached an agreement in principle to settle the Delaware Action for $12.5 million. A Stipulation and Agreement of Compromise, Settlement and Release, the Stipulation and Settlement Agreement, reflecting the terms of the proposed settlement was executed and filed with the Delaware Court of Chancery on July 5, 2022. On October 11, 2022, the Delaware Court of Chancery entered an Order and Final Judgment, or the Order, approving the Stipulation and Settlement Agreement in full after determining that the Stipulation and Settlement Agreement was fair, reasonable, and adequate. The Order provides for the full settlement, satisfaction, compromise and release of all claims that were asserted in the Delaware Action. The Order contains no admission of wrongdoing on the part of any of the Defendants.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On January 19, 2022, a purported stockholder of Ionis filed a stockholder derivative complaint in the Delaware Court of Chancery captioned Leo Shumacher, et al. v. Joseph Loscalzo, et al., C.A. No. 2022-0059, or the Shumacher Action. The complaint names Ionis&#8217; board of directors, or the Board, as defendants and names Ionis as a nominal defendant. The Shumacher Action Plaintiff asserts a breach of fiduciary duty claim against the Board for awarding and receiving allegedly excessive compensation. The Shumacher Action Plaintiff also asserts an unjust enrichment claim against the non-executive directors as a result of the compensation they received. The complaint seeks, among other things, damages, restitution, attorneys&#8217; fees and costs, and such other relief as deemed just and proper by the court. On March 18, 2022, Ionis and the Board moved to dismiss the complaint. On May 24, 2022, the parties entered into a Stipulation and Agreement of Compromise, Settlement and Release.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On May 25, 2022, another purported stockholder of Ionis filed a stockholder derivative complaint also in the Delaware Court of Chancery captioned Robert S. Cohen, et al. v. Joseph Loscalzo, et al., C.A. No. 2022-0453, or the Cohen Action. The complaint names the Board as defendants and names Ionis as a nominal defendant. The Cohen Action Plaintiff asserts claims for breach of fiduciary duty, unjust enrichment, aiding and abetting breaches of fiduciary duty, and waste against the Board for awarding and receiving allegedly excessive non-executive director compensation for the years 2018, 2019, and 2020. On June 2, 2022, the Cohen Action Plaintiff filed a motion to consolidate the related Cohen Action and Shumacher Action. On July 5, 2022, the Court denied the motion to consolidate in favor of the settlement pending in the Shumacher Action.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On July 18, 2022, Ionis filed a Form 8-K disclosing the pending settlement and attaching the Notice of Pendency of Settlement of Action. On September 21, 2022, the Court held a hearing to consider whether the terms of the settlement should be approved, at which hearing the Cohen Action plaintiff objected to the settlement. At the conclusion of the hearing, the Court declined to approve the settlement and directed the parties to meet and confer on the issue of the scope of the release. We and our Board have denied, and continue to deny, any and all allegations of wrongdoing or liability asserted in the Shumacher and Cohen Actions.</div>
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<div><a id="ITEM1A"><!--Anchor--></a></div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">RISK FACTORS</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Investing in our securities involves a high degree of risk. You should carefully consider the following information about the risks described below, together with the other information contained in this report and in our other public filings in evaluating our business. If any of the following risks actually occur, our business could be materially harmed, and our financial condition and results of operations could be materially and adversely affected. As a result, the trading price of our securities could decline, and you might lose all or part of your investment. We have marked with an asterisk those risk factors that reflect substantive changes from the risk factors included in our Annual Report on Form 10-K for the year ended December 31, 2021.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Summary of Risk Factors</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are a number of risks related to our business and our securities. Some of the principal risks related to our business include the following:</div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the impact on our operations and financial condition from the effects of the COVID-19 pandemic;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to generate substantial revenue from the sale of our medicines;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our and our partners&#8217; ability to compete effectively;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the availability of adequate coverage and payment rates for our medicines;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to successfully manufacture our medicines;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to successfully develop and obtain marketing approvals for our medicines;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to secure and maintain effective corporate partnerships;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to sustain cash flows and achieve consistent profitability;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to protect our intellectual property;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to maintain the effectiveness of our personnel; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the other factors set forth below.</div></td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Related to the COVID-19 Pandemic</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our business could be materially adversely affected by the effects of health epidemics. To date, we believe the impacts of the recent COVID-19 pandemic on our business are limited and manageable.</div>
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<div style="text-align: justify; text-indent: 40.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our business could be materially adversely affected by health epidemics in regions where we or our partners are commercializing our medicines, have concentrations of clinical trial sites or other business operations, and could cause significant disruption in the operations of third-party manufacturers and contract research organizations upon whom we rely. For example, since December 2019, a novel strain of coronavirus, SARS-CoV-2, causing a disease referred to as COVID-19, has spread worldwide. In March 2020, the World Health Organization declared the COVID-19 outbreak a pandemic and the U.S. government imposed restrictions on travel between the U.S., Europe and certain other countries. In addition, the Governor of the State of California and the Governor of the Commonwealth of Massachusetts, the states in which our offices are located, each declared a state of emergency related to the spread of COVID-19 and issued executive orders that directed residents to stay at home.</div>
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<div style="text-align: justify; text-indent: 40.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In response to these public health directives and orders, in March 2020, we implemented work-from-home policies for most of our employees globally and generally suspended business-related travel.&#160; In the U.S., as vaccinations have become more widely available, states have lifted restrictions implemented as part of the pandemic response and reopened their economies. In June 2021, the Governor of California terminated the vast majority of executive actions that were put in place beginning in March 2020, leaving only a subset of provisions that facilitate the ongoing recovery. In May 2021, the Commonwealth of Massachusetts also lifted most of its pandemic restrictions. We continue to modify our policies for our employees in California, Massachusetts, and internationally to align with current local guidance.&#160; We believe the effects of these work-from-home and travel policies have had a limited impact on our business.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These public health directives and orders have impacted our and our partners&#8217; sales efforts. For example, some physician and hospital policies that have been put in place as a result of the COVID-19 pandemic restrict in-person access by third parties, which has in some cases impacted our commercialization efforts for TEGSEDI and WAYLIVRA. Additionally, Biogen has reported that it is monitoring the demand for SPINRAZA, including the duration and degree to which it might see delays in starting new patients on SPINRAZA due to hospitals diverting resources necessary to administer SPINRAZA to care for COVID-19 patients. These and similar, and perhaps more severe, disruptions in our or our partner&#8217;s commercial operations could materially impact our business, operating results and financial condition in the future.</div>
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<div style="text-align: justify; text-indent: 40.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Quarantines, shelter-in-place, executive and similar government orders, or the perception that such orders, shutdowns or other restrictions on the conduct of business operations could occur, could impact personnel at third-party manufacturing facilities in the U.S. and other countries, or the availability or cost of materials, which would disrupt our supply chain.&#160; Recently there have been major disruptions to the global supply chain due to the COVID-19 pandemic. To date, we have not experienced any significant consequences to our business as a result of the current supply chain disruptions, but could in the future if such disruptions persist or worsen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have experienced impacts to our clinical trial operations due to the COVID-19 pandemic; however, we believe such impacts are limited and manageable. Some examples of these impacts include:</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">delays in clinical site initiation, site monitoring and patient enrollment due to restrictions imposed as a result of the COVID-19 pandemic;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, in March 2020, we instituted a temporary suspension of enrollment for new subjects in our Phase 3 studies of eplontersen based on advice from our trial advisory committee; however, enrollment has resumed.</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">some patients have not been able to meet protocol requirements, as quarantines have impeded patient movement and interrupted healthcare services;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">delays in site initiations due to principle investigators and site staff focusing on and prioritizing COVID-19 patient care; and</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">delays in necessary interactions with regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or forced furlough of government or contractor personnel.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, some of our partners have experienced impacts to their clinical trial operations as a result of the COVID-19 pandemic. For example, in December 2021, Novartis announced that enrollment for the Phase 3 HORIZON study had been delayed due to the COVID-19 pandemic.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The spread of COVID-19 has caused a broad impact globally. While the potential economic impact brought by, and the duration of, the COVID-19 pandemic may be difficult to assess or predict, it could result in significant disruption of global financial markets, reducing our ability to access capital, which could in the future negatively affect our liquidity. In addition, a recession or market correction resulting from the spread of COVID-19 could materially affect our business and has and could continue to affect the value of our securities.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The global COVID-19 pandemic continues to rapidly evolve. While we believe we have not yet experienced material adverse effects to our business as a result of the COVID-19 pandemic, the ultimate impact of the COVID-19 pandemic or a similar health epidemic is highly uncertain and subject to change. As such, we do not yet know the full extent of delays or impacts on our business, our clinical trials, healthcare systems or the global economy as a whole. However, these effects could have a material impact on our operations, and we will continue to monitor the COVID-19 pandemic closely.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Related to the Commercialization of our Medicines</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We have limited experience as a company in commercializing medicines and we will have to invest significant resources to develop these capabilities. If we are unable to establish effective marketing, sales, market access, distribution, and related functions, or enter into agreements with third parties to commercialize our medicines, we may not be able to generate revenue from our medicines.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have limited experience as a company in commercializing medicines and we will have to invest significant financial and management resources to develop the infrastructure required to successfully commercialize our medicines. There are significant risks involved in building and managing a sales organization, including our ability to hire, retain and incentivize qualified individuals, generate sufficient sales leads, provide adequate training to sales and marketing personnel, and effectively manage a geographically dispersed sales and marketing team. We will also need to scale-up existing internal support functions to aid our commercialization efforts, in particular, regulatory affairs and medical affairs. Any failure to effectively build or maintain the infrastructure required to successfully commercialize our medicines, including our sales, marketing, market access, distribution, and related capabilities, or scale-up our existing support functions, could adversely impact the revenue we generate from our medicines. In addition, if we choose to rely on third parties to assist us in commercializing our medicines, we may not be able to enter into collaborations or hire consultants or external service providers on acceptable financial terms, or at all.&#160; If we do engage third parties to assist us in the commercialization of our medicines, our product revenues and profitability may be lower than if we commercialized such medicines ourselves.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the market does not accept our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, we are not likely to generate substantial revenues or become consistently profitable.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Even if our medicines are authorized for marketing, our success will depend upon the medical community, patients and third-party payers accepting our medicines as medically useful, cost-effective, safe and convenient. Even when the FDA or foreign regulatory authorities authorize our or our partners&#8217; medicines for commercialization, doctors may not prescribe our medicines to treat patients. Furthermore, we and our partners may not successfully commercialize additional medicines.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally, in many of the markets where we or our partners may sell our medicines in the future, if we or our partners cannot agree with the government or other third-party payers regarding the price we can charge for our medicines, then we may not be able to sell our medicines in that market. Similarly, cost control initiatives by governments or third-party payers could decrease the price received for our medicines or increase patient coinsurance to a level that makes our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, economically unviable. If the pricing of any of our medicines decreases for any reason, it will reduce our revenue for such medicine. For example, Biogen has disclosed that SPINRAZA revenue has decreased in part due to lower pricing in the U.S. and certain rest of world markets.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The degree of market acceptance for our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, depends upon a number of factors, including the:</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">receipt and scope of marketing authorizations;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">establishment and demonstration in the medical and patient community of the efficacy and safety of our medicines and their potential advantages over competing products;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cost and effectiveness of our medicines compared to other available therapies;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">patient convenience of the dosing regimen for our medicines; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">reimbursement policies of government and third-party payers.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on the profile of our medicines, physicians, patients, patient advocates, payers or the medical community in general may not accept or use any medicines that we may develop.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, TEGSEDI requires periodic blood and urine monitoring, is available in the U.S. only through a REMS program, and the product label in the U.S. has a boxed warning for thrombocytopenia and glomerulonephritis. Our main competitors in the U.S. market for TEGSEDI are patisiran and vutrisiran, both marketed by Alnylam Pharmaceuticals, Inc. Neither patisiran nor vutrisiran has a boxed warning nor does either require use of a REMS program. Additionally, the product label for WAYLIVRA in the European Union, or EU, requires regular blood monitoring. In each case, these label requirements have negatively affected our ability to attract and retain patients for these medicines. If we or our partner cannot effectively maintain patients on TEGSEDI or WAYLIVRA, including due to limitations or restrictions on the ability to conduct periodic blood and urine monitoring of our patients as a result of the COVID-19 pandemic, we may not be able to generate substantial revenue from TEGSEDI or WAYLIVRA sales.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we or our partners fail to compete effectively, our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, will not generate significant revenues.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our competitors engage in drug discovery throughout the world, are numerous, and include, among others, major pharmaceutical companies and specialized biopharmaceutical firms. Other companies are engaged in developing antisense technology. Our competitors may succeed in developing medicines that are:</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">priced lower than our medicines;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">reimbursed more favorably by government and other third-party payers than our medicines;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">safer than our medicines;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">more effective than our medicines; or</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">more convenient to use than our medicines.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These competitive developments could make our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, obsolete or non-competitive.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certain of our partners are pursuing other technologies or developing other medicines either on their own or in collaboration with others, including our competitors, to treat the same diseases our own collaborative programs target. Competition may negatively impact a partner&#8217;s focus on and commitment to our medicines and, as a result, could delay or otherwise negatively affect the commercialization of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Many of our competitors have substantially greater financial, technical and human resources than we do. In addition, many of these competitors have significantly greater experience than we do in conducting preclinical testing and human clinical studies of new pharmaceutical products, in obtaining FDA and other regulatory authorizations of such products and in commercializing such products. Accordingly, our competitors may succeed in obtaining regulatory authorization for products earlier than we do.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are several pharmaceutical and biotechnology companies engaged in the development or commercialization in certain geographic markets of products against targets that are also targets of products in our development pipeline. For example:</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Onasemnogene abeparvovec and risdiplam compete with SPINRAZA;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patisiran, tafamidis, tafamidis meglumine and vutrisiran compete with TEGSEDI and could compete with eplontersen;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Acoramidis could compete with TEGSEDI and </span>eplontersen;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ARO-APOC3, lomitapide, evinacumab, BIO89-100, and gemcabene could compete with WAYLIVRA and olezarsen;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AMG890 could compete with pelacarsen;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Arimoclomol, ultomiris, mastinib and trehalose could compete with tofersen; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lanadelumab-flyo, C1 esterase inhibitor, berotralstat, C1 esterase inhibitor subcutaneous, garadacimab, KVD824, and NTLA-2002 could compete with donidalorsen.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA injection for intrathecal use is an antisense medicine indicated for the treatment of SMA patients of all ages approved in over 50 countries. Specifically, SPINRAZA faces competition from onasemnogene abeparvovec, a gene therapy product that was approved in the U.S. in May 2019 and in the EU in May 2020 for the treatment of SMA, as well as risdiplam, an oral product for the treatment of SMA that was approved in the U.S. in August 2020 and in the EU in March 2021. Biogen has disclosed that SPINRAZA revenue has decreased primarily due to a reduction in demand as a result of increased competition and that future sales of SPINRAZA may be adversely affected by competing products</span>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally, companies that are developing medicines that target the same patient populations as our medicines in development may compete with us to enroll participants in the clinical trials for such medicines, which could make it more difficult for us to complete enrollment for these clinical trials.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our medicines could be subject to regulatory limitations following approval.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Following approval of a medicine, we and our partners must comply with comprehensive government regulations regarding the manufacture, marketing and distribution of medicines. Promotional communications regarding prescription medicines must be consistent with the information in the product&#8217;s approved labeling. We or our partners may not obtain the labeling claims necessary or desirable to successfully commercialize our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA and foreign regulatory bodies have the authority to impose significant restrictions on an approved medicine through the product label and on advertising, promotional and distribution activities. For example:</div>
<div><br /></div>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in the U.S., TEGSEDI&#8217;s label contains a boxed warning for thrombocytopenia and glomerulonephritis;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI requires periodic blood and urine monitoring; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in the U.S., TEGSEDI is available only through a REMS program.</div></td>
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<div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prescription medicines may be promoted only for the approved indications in accordance with the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.</div>
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<div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, when approved, the FDA or a foreign regulatory authority may condition approval on the performance of post-approval clinical studies or patient monitoring, which could be time consuming and expensive. For example, in connection with the conditional marketing approval for WAYLIVRA in the EU, we are required to conduct a post-authorization safety study to evaluate the safety of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. If the results of such post-marketing studies are not satisfactory, the FDA, EC or other foreign regulatory authority may withdraw marketing authorization or may condition continued marketing on commitments from us or our partners that may be expensive and time consuming to fulfill.</div>
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<div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we or others identify side effects after any of our medicines are on the market, or if manufacturing problems occur subsequent to regulatory approval, or if we, our manufacturers or our partners fail to comply with regulatory requirements, we or our partners may, among other things, lose regulatory approval and be forced to withdraw products from the market, need to conduct additional clinical studies, incur restrictions on the marketing, distribution or manufacturing of the product, and/or change the labeling of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on our collaboration with Biogen for the development and commercialization of SPINRAZA.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have entered into a collaborative arrangement with Biogen to develop and commercialize SPINRAZA. We entered into this collaboration primarily to:</div>
<div><br /></div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">fund our development activities for SPINRAZA;</div></td>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">seek and obtain regulatory approvals for SPINRAZA; and</div></td>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">successfully commercialize SPINRAZA.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are relying on Biogen to obtain additional regulatory approvals for SPINRAZA, generate additional clinical data for SPINRAZA, manufacture and successfully commercialize SPINRAZA. In general, we cannot control the amount and timing of resources that Biogen devotes to our collaboration. If Biogen fails to further develop SPINRAZA, obtain additional regulatory approvals for SPINRAZA, manufacture or commercialize SPINRAZA, or if Biogen&#8217;s efforts are not effective, our business may be negatively affected.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our collaboration with Biogen may not continue for various reasons. Biogen can terminate our collaboration at any time. If Biogen stops developing or commercializing SPINRAZA, we would have to seek or spend additional funding, and SPINRAZA&#8217;s commercialization may be harmed or delayed.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our collaboration with Biogen may not result in the continued successful commercialization of SPINRAZA. If Biogen does not continue to successfully commercialize SPINRAZA, we will receive limited revenues for SPINRAZA.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on our collaboration with AstraZeneca for the joint development and commercialization of eplontersen.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have entered into a collaborative arrangement with AstraZeneca to develop and commercialize eplontersen. Under the terms of the collaboration agreement, Ionis and AstraZeneca will co-develop and co-commercialize eplontersen in the U.S. and AstraZeneca will have the sole right to commercialize eplontersen in all other countries, except for certain Latin American countries. Prior to co-commercializing eplontersen in the U.S., we will need to negotiate a co-commercialization agreement with AstraZeneca to govern the parties&#8217; performance of co-commercialization, which agreement will include a commercial plan and budget. As a company we do not have experience with co-commercialization arrangements. We also do not have control over the amount and timing of resources that AstraZeneca devotes to our collaboration, particularly outside of the U.S. If the co-commercialization arrangement for eplontersen is not successful for any reason, eplontersen may not meet our commercial objectives and our revenues for eplontersen may be limited.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, a Joint Steering Committee, or JSC, having equal membership from us and AstraZeneca, and various subcommittees oversee and coordinate the development, manufacturing, commercialization and other exploitation activities for eplontersen in the U.S. by mutual agreement. If any subcommittee cannot reach unanimous agreement on any matter within its respective scope of authority, such matter may be referred to the JSC for resolution. If the JSC cannot come to a mutual agreement on any particular matter, this could delay our ability to develop or commercialize eplontersen.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We are relying on third parties to market, sell and distribute TEGSEDI and WAYLIVRA.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have entered into agreements with third parties to commercialize TEGSEDI and WAYLIVRA as follows</span>:</div>
<div><br /></div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we entered into a distribution agreement with Sobi to commercialize TEGSEDI in the U.S. and Canada;</div></td>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2020, we entered into a distribution agreement with Sobi to commercialize TEGSEDI and WAYLIVRA in Europe; and</div></td>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, we granted PTC the exclusive right to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries.</div></td>
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<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are relying on Sobi and PTC to effectively market, sell and distribute TEGSEDI and WAYLIVRA and have less control over sales efforts and may receive less revenue than if we commercialized TEGSEDI or WAYLIVRA by ourselves. If Sobi or PTC does not successfully commercialize TEGSEDI or WAYLIVRA, including as a result of delays or disruption caused by the COVID-19 pandemic, we may receive limited revenue for TEGSEDI or WAYLIVRA in the U.S., Canada, Europe, Latin America or certain Caribbean countries, which could adversely affect our business, prospects, financial condition and results of operations.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our operations are subject to additional healthcare laws.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our operations are subject to additional healthcare laws, including federal and state anti-kickback laws, false claims laws, transparency laws, such as the federal Sunshine Act, and health information privacy and security laws, which are subject to change at any time.&#160; For example, in November 2020, the U.S. Department of Health and Human Services issued a final rule modifying the anti-kickback law safe harbors for Medicare Part D plans, pharmacies, and pharmaceutical benefit managers. Efforts to ensure that our operations comply with current applicable healthcare laws and regulations involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. Penalties for violations of applicable healthcare laws and regulations may include significant civil, criminal and administrative penalties, damages, disgorgement, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and additional reporting requirements and oversight if we enter into a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws. In addition, violations may also result in reputational harm, diminished profits and future earnings</span>.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If government or other third-party payers fail to provide adequate coverage and payment rates for our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, our revenue will be limited.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In both domestic and foreign markets, sales of our current and future products will depend in part upon the availability of coverage and reimbursement from third-party payers. The majority of patients in the U.S. who would fit within our target patient populations for our medicines have their healthcare supported by a combination of Medicare coverage, other government health programs such as Medicaid, managed care providers, private health insurers and other organizations. Coverage decisions may depend upon clinical and economic standards that disfavor new medicines when more established or lower cost therapeutic alternatives are already available or subsequently become available. Assuming coverage is approved, the resulting reimbursement payment rates might not be enough to make our medicines affordable. Even if favorable coverage status and adequate reimbursement rates are attained, less favorable coverage policies and reimbursement rates may be implemented in the future. Accordingly, SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, will face competition from other therapies and medicines for limited financial resources. We or our partners may need to conduct post-marketing studies to demonstrate the cost-effectiveness of any future products to satisfy third-party payers. These studies might require us to commit a significant amount of management time and financial and other resources. Third-party payers may never consider our future products as cost-effective. Adequate third-party coverage and reimbursement might not be available to enable us to maintain price levels sufficient to realize an appropriate return on investment in product development.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Third-party payers, whether foreign or domestic, or governmental or commercial, are developing increasingly sophisticated methods of controlling healthcare costs. In addition, in the U.S., no uniform policy of coverage and reimbursement for medicines exists among third-party payers. Therefore, coverage and reimbursement for medicines can differ significantly from payer to payer. For example, the Affordable Care Act was passed in March 2010, and substantially changed the way healthcare is financed by both governmental and private insurers, and continues to significantly impact the U.S. pharmaceutical industry. There have been judicial and Congressional challenges to certain aspects of the Affordable Care Act, as well as efforts to repeal or replace certain aspects of the Affordable Care Act. It is unclear how future litigation and healthcare reform measures will impact the Affordable Care Act and our business.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Further, we believe that future coverage, reimbursement and pricing will likely be subject to increased restrictions both in the U.S. and in international markets. In the U.S., recent health reform measures have resulted in reductions in Medicare and other healthcare funding, and there have been several recent U.S. Congressional inquiries, legislation and executive orders designed to, among other things, reduce drug prices (e.g., by supporting drug price negotiation in Medicare Parts B and D, with those negotiated prices also available to commercial plans, and progressing legislation to slow price increases over time on existing drugs), increase competition (e.g., by supporting legislation to speed the entry of biosimilar and generic drugs, including shortening the period of exclusivity, policies in Medicare Part B to increase the prescribing of biosimilars by physicians, and a prohibition on &#8220;pay-for-delay&#8221; agreements and anti-competitive practices by drug manufacturers), lower out-of-pocket drug costs for patients (e.g., by capping Medicare Part D beneficiary out-of-pocket pharmacy expenses), and foster scientific innovation to promote better health care and improved health (e.g., by investing in public and private research and incentivizing the market to promote discovery of valuable and accessible new treatments). In addition, on August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (&#8220;IRA&#8221;) into law, which among other things, (i) allows the U.S. Department of Health and Human Services to negotiate the price of certain single-source drugs and biologics covered under Medicare and (ii) imposes rebates under Medicare Part B and Medicare Part D. These provisions will take effect progressively starting in 2023, although they may be subject to legal challenges. It is currently unclear how the IRA will be effectuated but it is likely to have a significant impact on the pharmaceutical industry.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Third-party coverage and reimbursement for medicines may not be available or adequate in either the U.S. or international markets, and third-party payers, whether foreign or domestic, or governmental or commercial, may allocate their resources to address the COVID-19 pandemic or experience delays or disruptions in their ability to devote resources to coverage and reimbursement matters related to our products or medicines as a result of the COVID-19 pandemic, which would negatively affect the potential commercial success of our products, our revenue and our profits.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we are not successful in expanding our manufacturing capabilities or cannot manufacture our medicines or contract with a third party to manufacture our medicines at costs that allow us to charge competitive prices to buyers, we cannot market our products profitably.*</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To successfully commercialize any of our medicines, we would need to optimize and manage large-scale commercial manufacturing capabilities either on a standalone basis or through a third-party manufacturer. As our drug development and commercial pipeline increases and matures, we will have a greater need for clinical trial and commercial manufacturing capacity. To that end, we have plans to construct a new manufacturing facility in Oceanside, California that will expand our manufacturing infrastructure. We will incur substantial expenditures to build our new manufacturing facility and, following its completion, will likely need to hire and train additional staff to operate the facility. If we are not successful in executing this expansion, it could limit our ability to meet our manufacturing requirements and commercial objectives in the future.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We rely on third-party manufacturers to supply the drug substance and drug product for TEGSEDI and drug product for WAYLIVRA. Any delays or disruption to our own or third-party commercial manufacturing capabilities, including any interruption to our supply chain as a result of the COVID-19 pandemic or the ongoing war between Russia and Ukraine, could limit the commercial success of our medicines.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally, we have limited experience manufacturing pharmaceutical products of the chemical class represented by our medicines, called oligonucleotides, on a commercial scale for the systemic administration of a medicine. There are a small number of suppliers for certain capital equipment and raw materials that we use to manufacture our medicines, and some of these suppliers will need to increase their scale of production to meet our projected needs for commercial manufacturing. Further, we must continue to improve our manufacturing processes to allow us to reduce our drug costs. We or our partners may not be able to manufacture our medicines at a cost or in quantities necessary to make commercially successful products.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Also, manufacturers, including us, must adhere to the FDA&#8217;s cGMP regulations and similar regulations in foreign countries, which the applicable regulatory authorities enforce through facilities inspection programs. We, our partners and our contract manufacturers may not comply or maintain compliance with cGMP, or similar foreign regulations. Non-compliance could significantly delay or prevent receipt of marketing authorizations for our medicines, including authorizations for SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, or result in enforcement action after authorization that could limit the commercial success of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Related to the Development and Regulatory Approval of our Medicines</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we or our partners fail to obtain regulatory approval for our medicines and additional approvals for SPINRAZA, TEGSEDI and WAYLIVRA, we or our partners cannot sell them in the applicable markets.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We cannot guarantee that any of our medicines will be considered safe and effective or will be approved for commercialization. In addition, it is possible that SPINRAZA, TEGSEDI and WAYLIVRA may not be approved in additional markets or for additional indications. We and our partners must conduct time-consuming, extensive and costly clinical studies to demonstrate the safety and efficacy of each of our medicines before they can be approved or receive additional approvals for sale. We and our partners must conduct these studies in compliance with FDA regulations and with comparable regulations in other countries.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partners may not obtain necessary regulatory approvals on a timely basis, if at all, for our medicines. It is possible that regulatory agencies will not approve our medicines for marketing or SPINRAZA, TEGSEDI or WAYLIVRA in additional markets or for additional indications. If the FDA or another regulatory agency believes that we or our partners have not sufficiently demonstrated the safety or efficacy of any of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, or our medicines in development, the agency will not approve the specific medicine or will require additional studies, which can be time consuming and expensive and will delay or harm commercialization of the medicine. For example, in August 2018 we received a complete response letter from the FDA regarding the new drug application for WAYLIVRA in which the FDA determined that the safety concerns identified with WAYLIVRA in our clinical development program outweighed the expected benefits of triglyceride lowering in patients with FCS. We also received a Non-W from Health Canada for WAYLIVRA in November 2018.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA or other comparable foreign regulatory authorities can delay, limit or deny approval of a medicine for many reasons, including:</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may disagree with the design or implementation of our clinical studies;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners may be unable to demonstrate to the satisfaction of the FDA or other regulatory authorities that a medicine is safe and effective for any indication;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may not accept clinical data from studies conducted at clinical facilities that have deficient clinical practices or that are in countries where the standard of care is potentially different from the U.S.;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners may be unable to demonstrate that our medicine&#8217;s clinical and other benefits outweigh its safety risks to support approval;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may disagree with the interpretation of data from preclinical or clinical studies;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may find deficiencies in the manufacturing processes or facilities of third-party manufacturers who manufacture clinical and commercial supplies for our medicines, or may delay the inspection of such facilities due to restrictions related to the COVID-19 pandemic; and</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the approval policies or regulations of such authorities or their prior guidance to us or our partners during clinical development may significantly change in a manner rendering our clinical data insufficient for approval.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Failure to receive marketing authorization for our medicines, or failure to receive additional marketing authorizations for SPINRAZA, TEGSEDI or WAYLIVRA, or delays in these authorizations, could prevent or delay commercial introduction of the medicine, and, as a result, could negatively impact our ability to generate revenue from product sales.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We may not be able to benefit from orphan drug designation for our medicines.</div>
<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the U.S., under the Orphan Drug Act, the FDA may designate a medicine as an orphan drug if it is intended to treat a rare disease or condition affecting fewer than 200,000 individuals in the U.S. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process, but it can provide financial incentives, such as tax advantages and user-fee waivers, as well as longer regulatory exclusivity periods. The FDA has granted orphan drug designation to eplontersen for the treatment of patients with transthyretin-mediated amyloidosis and to ION582 for the treatment of patients with Angelman syndrome. The FDA and EMA have granted orphan drug designation to TEGSEDI for the treatment of patients with ATTRv-PN, to WAYLIVRA for the treatment of patients with FCS, and to tominersen for the treatment of patients with HD. In addition, the EMA has granted orphan drug designation to WAYLIVRA for the treatment of patients with FPL. Even if approval is obtained on a medicine that has been designated as an orphan drug, we may lose orphan drug exclusivity if the FDA or EMA determines that the request for designation was materially defective or if we cannot assure sufficient quantity of the applicable medicine to meet the needs of patients with the rare disease or condition, or if a competitor is able to gain approval for the same medicine in a safer or more effective form or that makes a major contribution to patient care. If we lose orphan drug exclusivity on any of our medicines, we may face increased competition and lose market share for such medicine.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the results of clinical testing indicate that any of our medicines are not suitable for commercial use, we may need to abandon one or more of our drug development programs.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug discovery and development has inherent risks and the historical failure rate for drugs is high. Antisense medicines are a relatively new approach to therapeutics. If we cannot demonstrate that our medicines are safe and effective for human use in the intended indication, we may need to abandon one or more of our drug development programs.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Even if our medicines are successful in preclinical and human clinical studies, the medicines may not be successful in late-stage clinical studies.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Successful results in preclinical or initial human clinical studies, including the Phase 2 results for some of our medicines in development, may not predict the results of subsequent clinical studies. If any of our medicines in Phase 3 clinical studies, including the studies of eplontersen, olezarsen, donidalorsen, ION363, pelacarsen and tofersen, do not show sufficient efficacy in patients with the targeted indication, or if such studies are discontinued for any other reason, it could negatively impact our development and commercialization goals for these medicines and our stock price could decline.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the past, we have invested in clinical studies of medicines that have not met the primary clinical endpoints in their Phase 3 studies or have been discontinued for other reasons. For example, in October 2021, Biogen reported that tofersen did not meet the primary clinical endpoint in the Phase 3 VALOR study; however, trends favoring tofersen were seen across multiple secondary and exploratory measures of disease activity and clinical function. In addition, in March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest Huntington&#8217;s disease based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded Independent Data Monitoring Committee. Similar results could occur in clinical studies for our other medicines, including the studies of eplontersen, olezarsen, donidalorsen, ION363 and pelacarsen.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are a number of factors that could cause a clinical study to fail or be delayed, including:</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the clinical study may produce negative or inconclusive results;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">regulators may require that we hold, suspend or terminate clinical research for noncompliance with regulatory requirements;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we, our partners, the FDA or foreign regulatory authorities could suspend or terminate a clinical study due to adverse side effects of a medicine on subjects or lack of efficacy in the trial;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we, or our partners, may decide, or regulators may require us, to conduct additional preclinical testing or clinical studies;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">enrollment in our clinical studies may be slower than we anticipate;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners, including our independent clinical investigators, contract research organizations and other third-party service providers on which we rely, may not identify, recruit and train suitable clinical investigators at a sufficient number of study sites or timely enroll a sufficient number of study subjects in the clinical study;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the institutional review board for a prospective site might withhold or delay its approval for the study;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">people who enroll in the clinical study may later drop out due to adverse events, a perception they are not benefiting from participating in the study, fatigue with the clinical study process or personal issues;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a clinical study site may deviate from the protocol for the study;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the cost of our clinical studies may be greater than we anticipate;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our partners may decide not to exercise any existing options to license and conduct additional clinical studies for our medicines; and</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the supply or quality of our medicines or other materials necessary to conduct our clinical studies may be insufficient, inadequate or delayed.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The COVID-19 pandemic could make some of these factors more likely to occur.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, our current medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, are chemically similar to each other. As a result, a safety observation we encounter with one of our medicines could have, or be perceived by a regulatory authority to have, an impact on a different medicine we are developing. This could cause the FDA or other regulators to ask questions or take actions that could harm or delay our ability to develop and commercialize our medicines or increase our costs. For example, the FDA or other regulatory agencies could request, among other things, any of the following regarding one of our medicines: additional information or commitments before we can start or continue a clinical study, protocol amendments, increased safety monitoring, additional product labeling information, and post-approval commitments. This happened in connection with the conditional marketing approval for WAYLIVRA in the EU, as the EC is requiring us to conduct a post-authorization safety study to evaluate the safety of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. We have ongoing post-marketing studies for WAYLIVRA and TEGSEDI and an EAP for WAYLIVRA. Adverse events or results from these studies or the EAPs could negatively impact our pending or future marketing approval applications for WAYLIVRA and TEGSEDI in patients with FCS or ATTRv-PN, respectively, or the commercial opportunity for WAYLIVRA or TEGSEDI.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Any failure or delay in our clinical studies, including the studies of tofersen, pelacarsen, eplontersen, olezarsen, donidalorsen, and ION363, could reduce the commercial potential or viability of our medicines.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on third parties to conduct our clinical studies for our medicines and any failure of those parties to fulfill their obligations could adversely affect our development and commercialization plans.*</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We depend on independent clinical investigators, contract research organizations and other third-party service providers to conduct our clinical studies for our medicines and expect to continue to do so in the future. For example, we use clinical research organizations, such as Icon Clinical Research Limited, Syneos Health, Inc., Thermo Fisher Scientific Inc. and Medpace for the clinical studies for our medicines, including eplontersen, olezarsen, donidalorsen, ION363, pelacarsen and tofersen. We rely heavily on these parties for successful execution of our clinical studies, but do not control many aspects of their activities. For example, the investigators are not our employees. However, we are responsible for ensuring that these third parties conduct each of our clinical studies in accordance with the general investigational plan and approved protocols for the study. Third parties may not complete activities on schedule or may not conduct our clinical studies in accordance with regulatory requirements or our stated protocols. For example, some of our key vendors are experiencing labor shortages, which could impact their ability to perform services for us for certain of our clinical trials. The failure of these third parties to carry out their obligations, including as a result of delays or disruption caused by the COVID-19 pandemic that may affect the third party&#8217;s ability to conduct the clinical studies for our medicines, or a termination of our relationship with these third parties, could delay or prevent the development, marketing authorization and commercialization of our medicines or additional marketing authorizations for TEGSEDI and WAYLIVRA.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, while we do not have any clinical trial sites in Ukraine, we do have a limited number of clinical trial sites in Russia and surrounding countries that may be impacted by the ongoing war between Russia and Ukraine, and could result in difficulties enrolling or completing our clinical trials in such areas on schedule. Furthermore, the U.S. and its European allies have imposed significant sanctions against Russia, including regional embargoes, full blocking sanctions, and other restrictions targeting major Russian financial institutions. The U.S. government has also indicated it will consider imposing additional sanctions and other similar measures in the near future. Our ability to conduct clinical trials in Russia may become restricted under applicable sanctions laws, which would require us to identify alternative trial sites, and could increase our costs and delay the clinical development of certain of our medicines.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Since corporate partnering is a significant part of our strategy to fund the advancement and commercialization of our development programs, if any of our collaborative partners fail to fund our collaborative programs, or if we cannot obtain additional partners, we may have to delay or stop progress on our drug development programs.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To date, corporate partnering has played a significant role in our strategy to fund our development programs and to add key development resources. We plan to continue to rely on additional collaborative arrangements to develop and commercialize many of our unpartnered medicines. However, we may not be able to negotiate favorable collaborative arrangements for these drug programs. If we cannot continue to secure additional collaborative partners, our revenues could decrease and the development of our medicines could suffer.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our corporate partners are developing and/or funding many of the medicines in our development pipeline. For example, we are relying on:</div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AstraZeneca for the joint development and funding of eplontersen;</div></td>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis for development and funding of pelacarsen;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen for development and funding of tofersen; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Roche for development and funding of tominersen.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If any of these pharmaceutical companies stops developing and/or funding these medicines, our business could suffer and we may not have, or be willing to dedicate, the resources available to develop these medicines on our own. Our collaborators can terminate their relationships with us under certain circumstances, many of which are outside of our control. For example, after a review of data from the global Phase 2b study of vupanorsen, Pfizer decided to discontinue the clinical development program for vupanorsen.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Even with funding from corporate partners, if our partners do not effectively perform their obligations under our agreements with them, it would delay or stop the progress of our drug development and commercial programs.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to receiving funding, we enter into collaborative arrangements with third parties to:</div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">conduct clinical studies;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">seek and obtain marketing authorizations; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">manufacture, market and sell our medicines.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Once we have secured a collaborative arrangement to further develop and commercialize one of our drug development programs, such as our collaborations with AstraZeneca, Biogen, GSK, Novartis, and Roche, these collaborations may not continue or result in commercialized medicines, or may not progress as quickly as we first anticipated.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, a collaborator such as AstraZeneca, Biogen, GSK, Novartis, or Roche, could determine that it is in its financial interest to:</div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">pursue alternative technologies or develop alternative products that may be competitive with the medicine that is part of the collaboration with us;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">pursue higher-priority programs or change the focus of its own development programs; or</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">choose to devote fewer resources to our medicines than it does for its own medicines.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If any of these occur, it could affect our partner&#8217;s commitment to the collaboration with us and could delay or otherwise negatively affect the commercialization of our medicines, including SPINRAZA, pelacarsen, tofersen, and eplontersen.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we do not progress in our programs as anticipated, the price of our securities could decrease.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For planning purposes, we estimate and may disclose the timing of a variety of clinical, regulatory and other milestones, such as when we anticipate a certain medicine will enter clinical trials, when we anticipate completing a clinical study, or when we anticipate filing an application for, or obtaining, marketing authorization, or when we or our partners plan to commercially launch a medicine. We base our estimates on present facts and a variety of assumptions, many of which are outside of our control, including the COVID-19 pandemic. If we do not achieve milestones in accordance with our or our investors&#8217; or securities analysts&#8217; expectations, including milestones related to SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen, olezarsen, donidalorsen, ION363, pelacarsen and tofersen, the price of our securities could decrease.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Associated with our Businesses as a Whole</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our financial condition</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We have incurred losses, and our business will suffer if we fail to consistently achieve profitability in the future.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Because drug discovery and development requires substantial lead-time and money prior to commercialization, our expenses have generally exceeded our revenue since we were founded in January 1989. As of September 30, 2022, we had an accumulated deficit of approximately $1.4 billion and stockholders&#8217; equity of approximately $0.6 billion. Most of our historical losses resulted from costs incurred in connection with our research and development programs and from selling, general and administrative costs associated with our operations. Most of our income has come from collaborative arrangements, including commercial revenue from royalties and R&amp;D revenue, with additional income from research grants and the sale or licensing of our patents, as well as interest income. If we do not continue to earn substantial revenue, we may incur additional operating losses in the future. We may not successfully develop any additional medicines or achieve or sustain future profitability.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we fail to obtain timely funding, we may need to curtail or abandon some of our programs.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Many of our medicines are undergoing clinical studies or are in the early stages of research and development. Most of our drug programs will require significant additional research, development, manufacturing, preclinical and clinical testing, marketing authorizations, preclinical activities and commitment of significant additional resources prior to their successful commercialization. These activities will require significant cash. As of </span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we had cash, cash equivalents and short-term investments equal to $</span>2.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion. If we or our partners do not meet our goals to successfully commercialize our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, or to license certain medicines and proprietary technologies, we will need additional funding in the future. Our future capital requirements will depend on many factors, such as the following:</span></div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">successful commercialization of SPINRAZA, TEGSEDI and WAYLIVRA;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">additional marketing approvals for WAYLIVRA and TEGSEDI;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the profile and launch timing of our medicines, including eplontersen, olezarsen, donidalorsen, ION363, pelacarsen and tofersen;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">changes in existing collaborative relationships and our ability to establish and maintain additional collaborative arrangements;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">continued scientific progress in our research, drug discovery and development programs;</div></td>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the size of our programs and progress with preclinical and clinical studies;</div></td>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the time and costs involved in obtaining marketing authorizations;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">competing technological and market developments, including the introduction by others of new therapies that address our markets; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our manufacturing requirements and capacity to fulfill such requirements.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we need additional funds, we may need to raise them through public or private financing. Additional financing may not be available at all or on acceptable terms. If we raise additional funds by issuing equity securities, the shares of existing stockholders will be diluted and the price, as well as the price of our other securities, may decline. If adequate funds are not available or not available on acceptable terms, we may have to cut back on one or more of our research, drug discovery or development programs. Alternatively, we may obtain funds through arrangements with collaborative partners or others, which could require us to give up rights to certain of our technologies or medicines.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our intellectual property</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we cannot protect our patent rights or our other proprietary rights, others may compete more effectively against us.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our success depends to a significant degree upon whether we can continue to develop, secure and maintain intellectual property rights to proprietary products and services. However, we may not receive issued patents on any of our pending patent applications in the U.S. or in other countries and we may not be able to obtain, maintain or enforce our patents and other intellectual property rights which could impact our ability to compete effectively. In addition, the scope of any of our issued patents may not be sufficiently broad to provide us with a competitive advantage. Furthermore, other parties may successfully challenge, invalidate or circumvent our issued patents or patents licensed to us so that our patent rights do not create an effective competitive barrier or revenue source.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We cannot be certain that the U.S. Patent and Trademark Office, or U.S. PTO, and courts in the U.S. or the patent offices and courts in foreign countries will consider the claims in our patents and applications covering SPINRAZA, TEGSEDI, WAYLIVRA, or any of our medicines in development as patentable. Method-of-use patents protect the use of a product for the specified method. This type of patent does not prevent a competitor from making and marketing a product that is identical to our product for an indication that is outside the scope of the patented method. Moreover, even if competitors do not actively promote their product for our targeted indications, physicians may prescribe these products off-label. Although off-label prescriptions may infringe or contribute to the infringement of method-of-use patents, the practice is common and such infringement is difficult to prevent, even through legal action.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If we or any licensor partner loses or cannot obtain patent protection for SPINRAZA, TEGSEDI, WAYLIVRA, or any of our other medicines in development, it could have a material adverse impact on our business</span>.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intellectual property litigation could be expensive and prevent us from pursuing our programs.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time we have to defend our intellectual property rights. If we are involved in an intellectual property dispute, we may need to litigate to defend our rights or assert them against others. Disputes can involve arbitration, litigation or proceedings declared by the U.S. PTO or the International Trade Commission or foreign patent authorities. Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If a third party claims that our medicines or technology infringe its patents or other intellectual property rights, we may have to discontinue an important product or product line, alter our products and processes, pay license fees or cease certain activities. We may not be able to obtain a license to needed intellectual property on favorable terms, if at all. There are many patents issued or applied for in the biotechnology industry, and we may not be aware of patents or patent applications held by others that relate to our business. This is especially true since patent applications in the U.S. are filed confidentially for the first 18 months. Moreover, the validity and breadth of biotechnology patents involve complex legal and factual questions for which important legal issues remain.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our personnel</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If our management transition is not successful our business could suffer.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2020, Dr. Crooke, our founder and Chief Executive Officer, transitioned from Chief Executive Officer to Executive Chairman of our Board of Directors, and Dr. Monia, who was our Chief Operating Officer and a member of our team since our founding over 30 years ago, began serving as our Chief Executive Officer. Following the 2021 Annual Meeting of Stockholders, Dr. Crooke stepped down from the Board and now serves as a Strategic Advisor to us, providing strategic advice and continuing to participate in our scientific activities. In June 2021, Dr. Loscalzo, a member of our Board since February 2014, was appointed Chairman of the Board. If this transition is not successful, our business could suffer.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">The loss of key personnel, or the inability to attract and retain highly skilled personnel, could make it more difficult to run our business and reduce our likelihood of success.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are dependent on the principal members of our management and scientific staff. We do not have employment agreements with any of our executive officers that would prevent them from leaving us. The loss of our management and key scientific employees might slow the achievement of important research and development goals. It is also critical to our success that we recruit and retain qualified scientific personnel to perform research and development work. We may not be able to attract and retain skilled and experienced scientific personnel on acceptable terms because of intense competition for experienced scientists among many pharmaceutical and health care companies, universities and non-profit research institutions. In addition, failure to succeed in clinical studies may make it more challenging to recruit and retain qualified scientific personnel.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to taxes</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our ability to use our net operating loss carryovers and certain other tax attributes may be limited.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the Internal Revenue Code of 1986, as amended, or the Code, a corporation is generally allowed a deduction for net operating losses, or NOLs, carried over from a prior taxable year. Under the Code, we can carryforward our NOLs to offset our future taxable income, if any, until such NOLs are used or expire. The same is true of other unused tax attributes, such as tax credits.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the current U.S. federal income tax law, U.S. federal NOLs generated in taxable years beginning after December 31, 2017 may be carried forward indefinitely, but the deductibility of such U.S. federal NOLs in taxable years beginning after December 31, 2020 is limited to 80 percent of taxable income. It is uncertain if and to what extent various states will conform to current U.S. federal income tax law, and there may be periods during which states suspend or otherwise limit the use of NOLs for state income tax purposes.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, under Sections 382 and 383 of the Code, and corresponding provisions of state law, if a corporation undergoes an &#8220;ownership change,&#8221; which is generally defined as a greater than 50 percentage-point cumulative change, by value, in its equity ownership over a three-year period, the corporation&#8217;s ability to use its pre-change NOL carryforwards and other pre-change tax attributes to offset its post-change income or taxes may be limited. We may experience ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which may be outside of our control. If an ownership change occurs and our ability to use our NOL carryforwards or other tax attributes is materially limited, it would harm our future operating results by effectively increasing our future tax obligations. As a result of the Akcea Merger, we are subject to the separate return limitation year, or SRLY, rules. Under the SRLY rules, our utilization of Akcea&#8217;s pre-merger NOL and tax credit carryforwards is limited to the amount of income that Akcea contributes to our consolidated taxable income. The Akcea pre-merger tax attributes cannot be used to offset any of the income that Ionis contributes to our consolidated taxable income. In addition, at the state level, there may be periods during which the use of net operating losses is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our future taxable income could be impacted by changes in tax laws, regulations and treaties.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A change in tax laws, treaties or regulations, or their interpretation, of any country in which we operate could materially affect us.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We could be subject to additional tax liabilities.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are subject to U.S. federal, state, local and foreign income taxes, sales taxes in the U.S., withholding taxes and transaction taxes in foreign jurisdictions. Significant judgment is required in evaluating our tax positions and our worldwide provision for taxes. During the ordinary course of business, there are many activities and transactions for which the ultimate tax determination is uncertain. In addition, our tax obligations and effective tax rates could be adversely affected by changes in the relevant tax, accounting and other laws, regulations, principles and interpretations, including those relating to income tax nexus, by recognizing tax losses or lower than anticipated earnings in jurisdictions where we have lower statutory rates and higher than anticipated earnings in jurisdictions where we have higher statutory rates, by changes in foreign currency exchange rates, or by changes in the valuation of our deferred tax assets and liabilities. We may be audited in various jurisdictions, and such jurisdictions may assess additional taxes, sales taxes and value-added taxes against us. Although we believe our tax estimates are reasonable, the final determination of any tax audits or litigation could be materially different from our historical tax provisions and accruals, which could have a material adverse effect on our operating results or cash flows in the period for which a determination is made.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">General risk factors</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the price of our securities continues to be highly volatile, this could make it harder to liquidate your investment and could increase your risk of suffering a loss.*</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The market price of our common stock, like that of the securities of many other biopharmaceutical companies, has been and is likely to continue to be highly volatile. These fluctuations in our common stock price may significantly affect the trading price of our securities. During the 12 months preceding September 30, 2022, the market price of our common stock ranged from $48.82 to $25.04 per share. Many factors can affect the market price of our securities, including, for example, fluctuations in our operating results, announcements of collaborations, clinical study results, technological innovations or new products being developed by us or our competitors, the commercial success of our approved medicines, governmental regulation, marketing authorizations, changes in payers&#8217; reimbursement policies, developments in patent or other proprietary rights and public concern regarding the safety of our medicines.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Broad market factors may materially harm the market price of our common stock irrespective of our operating performance. For example, the COVID-19 pandemic has caused a significant disruption of global financial markets and has resulted in increased volatility in the trading price of our common stock. The global credit and financial markets may also be adversely affected by the ongoing war between Russia and Ukraine and measures taken in response thereto. In addition, industry factors may materially harm the market price of our common stock. NASDAQ, and the market for biotechnology companies in particular, have historically experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of the particular companies affected. The trading prices and valuations of these stocks, and of ours, may not be predictable. A loss of investor confidence in the market for biotechnology or pharmaceutical stocks or the stocks of other companies that investors perceive to be similar to us, the opportunities in the biotechnology and pharmaceutical market or the stock market in general, could depress our stock price regardless of our business, prospects, financial conditions or results of operations.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Provisions in our certificate of incorporation, convertible notes documents, call spread hedge transaction documents and Delaware law may prevent stockholders from receiving a premium for their shares.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our certificate of incorporation provides for classified terms for the members of our board of directors. Our certificate also includes a provision that requires at least 66 2/3 percent of our voting stockholders to approve a merger or certain other business transactions with, or proposed by, any holder of 15 percent or more of our voting stock, except in cases where certain directors approve the transaction or certain minimum price criteria and other procedural requirements are met.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our certificate of incorporation also requires that any action required or permitted to be taken by our stockholders must be taken at a duly called annual or special meeting of stockholders and may not be taken by written consent. In addition, only our board of directors, chairman of the board or chief executive officer can call special meetings of our stockholders. We have in the past, and may in the future, implement a stockholders&#8217; rights plan, also called a poison pill, which could make it uneconomical for a third party to acquire our company on a hostile basis. In addition, our board of directors has the authority to fix the rights and preferences of, and issue shares of preferred stock, which may have the effect of delaying or preventing a change in control of our company without action by our stockholders.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The provisions of our convertible senior notes could make it more difficult or more expensive for a third party to acquire us. Upon the occurrence of certain transactions constituting a fundamental change, holders of the notes will have the right, at their option, to require us to repurchase all of their notes or a portion of their notes, which may discourage certain types of transactions in which our stockholders might otherwise receive a premium for their shares over the then current market prices.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we completed a $632.5 million offering of 0% Notes and used a portion of the net proceeds from the issuance of the 0% Notes to repurchase $247.9 million of our 1% Notes for $257.0 million. In December 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of our existing 1% Notes to exchange $375.6 million of our 1% Notes for $439.3 million of our 0.125% Notes, and to issue $109.5 million of our 0.125% Notes. Additionally, in connection with the pricing of our 0% Notes and 0.125% Notes, we entered into call spread transactions in which we purchased note hedges and sold warrants. Terminating or unwinding the call spread transactions could require us to make substantial payments to the counterparties under those agreements or may increase our stock price. The costs or any increase in stock price that may arise from terminating or unwinding such agreements could make an acquisition of our company significantly more expensive to the purchaser.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These provisions, as well as Delaware law, including Section 203 of the Delaware General Corporation Law, and other of our agreements, may discourage certain types of transactions in which our stockholders might otherwise receive a premium for their shares over then current market prices, and may limit the ability of our stockholders to approve transactions that they think may be in their best interests.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Future sales of our common stock in the public market could adversely affect the trading price of our securities.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Future sales of substantial amounts of our common stock in the public market, or the perception that such sales could occur, could adversely affect trading prices of our securities. For example, we may issue approximately 17.5 million shares of our common stock upon conversion of our 0% Notes and 0.125% Notes, up to 10.9 million shares in connection with the warrant transactions we entered into in connection with the issuance of our 0% Notes, and up to 6.6 million shares in connection with the warrant transactions we entered into in connection with the issuance of our 0.125% Notes, in each case subject to customary anti-dilution adjustments. The addition of any of these shares into the public market may have an adverse effect on the price of our securities.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, pursuant to the call spread transactions we entered into in connection with the pricing of our 0% Notes and 0.125% Notes, the counterparties are likely to modify their hedge positions from time to time at or prior to the conversion or maturity of the notes by purchasing and selling shares of our common stock, other of our securities, or other instruments, including over-the-counter derivative instruments, that they may wish to use in connection with such hedging, which may have a negative effect on the conversion value of those notes and an adverse impact on the trading price of our common stock. The call spread transactions are expected generally to reduce potential dilution to holders of our common stock upon any conversion of our 0% Notes or 0.125% Notes or offset any cash payments we are required to make in excess of the principal amount of the converted 0% Notes or 0.125% Notes, as the case may be. However, the warrant transactions could separately have a dilutive effect to the extent that the market value per share of our common stock exceeds the applicable strike price of the warrants.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We are exposed to potential product liability claims, and insurance against these claims may not be available to us at a reasonable rate in the future or at all.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our business exposes us to potential product liability risks that are inherent in the testing, manufacturing, marketing and sale of therapeutic products, including potential product liability claims related to SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development. We have clinical study insurance coverage and commercial product liability insurance coverage. However, this insurance coverage may not be adequate to cover claims against us, or be available to us at an acceptable cost, if at all. Regardless of their merit or eventual outcome, product liability claims may result in decreased demand for our medicines, injury to our reputation, withdrawal of clinical study volunteers and loss of revenues. Thus, whether or not we are insured, a product liability claim or product recall may result in losses that could be material.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We are dependent on information technology systems, infrastructure and data, which exposes us to data security risks.*</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are dependent upon our own and third-party information technology systems, infrastructure and data, including mobile technologies, to operate our business. The multitude and complexity of our computer systems may make them vulnerable to service interruption or destruction, disruption of data integrity, malicious intrusion, or random attacks. Likewise, data privacy or security incidents or breaches by employees or others may pose a risk that sensitive data, including our intellectual property, trade secrets or personal information of our employees, patients, customers or other business partners may be exposed to unauthorized persons or to the public. Cyber-attacks are increasing in their frequency, sophistication and intensity, with third-party phishing and social engineering attacks in particular increasing during the COVID-19 pandemic. In addition, the number and frequency of cybersecurity events globally may be heightened during times of geopolitical tension or instability between countries, including, for example, the ongoing war between Russia and Ukraine, as a result of which several companies (not including Ionis) have reported recent cybersecurity events.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cyber-attacks could include the deployment of harmful malware, denial-of-service, social engineering and other means to affect service reliability and threaten data confidentiality, integrity and availability. Our business partners face similar risks and any security breach of their systems could adversely affect our security posture. A security breach or privacy violation that leads to disclosure or modification of or prevents access to patient information, including personally identifiable information or protected health information, could harm our reputation, compel us to comply with federal and state breach notification laws and foreign law equivalents, subject us to financial penalties and mandatory and costly corrective action, require us to verify the correctness of database contents and otherwise subject us to litigation or other liability under laws and regulations that protect personal data, any of which could disrupt our business and result in increased costs or loss of revenue. Moreover, the prevalent use of mobile devices that access confidential information increases the risk of data security breaches, which could lead to the loss of confidential information, trade secrets or other intellectual property. While we have invested, and continue to invest, in the protection of our data and information technology infrastructure, our efforts may not prevent service interruptions or identify breaches in our systems that could adversely affect our business and operations and result in the loss of critical or sensitive information, which could result in financial, legal, business or reputational harm to us. In addition, our liability insurance may not be sufficient in type or amount to cover us against claims related to security breaches, cyber-attacks and other related breaches.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Because we use biological materials, hazardous materials, chemicals and radioactive compounds, if we do not comply with laws regulating the protection of the environment and health and human safety, our business could be adversely affected.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and manufacturing activities involve the use of potentially harmful biological materials as well as materials, chemicals and various radioactive compounds that could be hazardous to human health and safety or the environment. We store most of these materials and various wastes resulting from their use at our facilities in Carlsbad, California pending ultimate use and disposal. We cannot completely eliminate the risk of contamination, which could cause:</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In such an event, we may be held liable for any resulting damages, and any liability could exceed our resources. Although we carry insurance in amounts and types that we consider commercially reasonable, we do not have insurance coverage for losses relating to an interruption of our research, development or manufacturing efforts caused by contamination, and the coverage or coverage limits of our insurance policies may not be adequate. If our losses exceed our insurance coverage, our financial condition would be adversely affected.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our business may be adversely affected by climate change, extreme weather events, earthquakes, pandemics, war, civil or political unrest, terrorism or other catastrophic events.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In recent years, extreme weather events and changing weather patterns have become more common. As a result, we are potentially exposed to varying natural disaster or extreme weather risks such as hurricanes, tornadoes, fires, droughts, floods, or other events that may result from the impact of climate change on the environment. The potential impacts of climate change may also include increased operating costs associated with additional regulatory requirements and investments in reducing energy, water use and greenhouse gas emissions. In addition, we currently manufacture most of our research and clinical supplies in a manufacturing facility located in Carlsbad, California and will move such manufacturing to our new facility in Oceanside, California once it is built. We manufacture the finished drug product for TEGSEDI and WAYLIVRA at third-party contract manufacturers. Biogen manufactures the finished drug product for SPINRAZA. The facilities and the equipment we, our partners and our contract manufacturers use to research, develop and manufacture our medicines would be costly to replace and could require substantial lead time to repair or replace. Our facilities or those of our partners or contract manufacturers may be harmed by natural disasters or other events outside our control, such as earthquakes, pandemics, war, civil or political unrest, deliberate acts of sabotage, terrorism or industrial accidents such as fire and explosion, whether due to human or equipment error, and if such facilities are affected by a disaster or other event, our development and commercialization efforts would be delayed. Although we possess property damage and business interruption insurance coverage, this insurance may not be sufficient to cover all of our potential losses and may not continue to be available to us on acceptable terms, or at all. In addition, our development and commercialization activities could be harmed or delayed by a shutdown of the U.S. government, including the FDA.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our business is subject to changing regulations for corporate governance and public disclosure that has increased both our costs and the risk of noncompliance.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Each year we are required to evaluate our internal control systems in order to allow management to report on, and our Independent Registered Public Accounting Firm to attest to, our internal controls as required by Section 404 of the Sarbanes-Oxley Act. As a result, we continue to incur additional expenses and divert our management&#8217;s time to comply with these regulations. In addition, if we cannot continue to comply with the requirements of Section 404 in a timely manner, we might be subject to sanctions or investigation by regulatory authorities, such as the SEC, the Public Company Accounting Oversight Board, or PCAOB, or The Nasdaq Global Select Market. Any such action could adversely affect our financial results and the market price of our common stock.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The SEC and other regulators have continued to adopt new rules and regulations and make additional changes to existing regulations that require our compliance. On July 21, 2010, the Dodd-Frank Wall Street Reform and Protection Act, or the Dodd-Frank Act, was enacted. There are significant corporate governance and executive compensation-related provisions in the Dodd-Frank Act that require the SEC to adopt, or where the SEC has adopted, additional rules and regulations in these areas such as &#8220;say on pay&#8221; and proxy access. Stockholder activism, the current political environment and the current high level of government intervention and regulatory reform may lead to substantial new regulations and disclosure obligations, which may lead to additional compliance costs and impact the manner in which we operate our business.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Negative conditions in the global credit markets and financial services and other industries may adversely affect our business.*</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The global credit markets, the financial services industry, the U.S. capital markets, and the U.S. economy as a whole have recently experienced substantial turmoil and uncertainty characterized by unprecedented intervention by the U.S. federal government in response to the COVID-19 pandemic. In addition, the global credit and financial markets may be adversely affected by the ongoing war between Russia and Ukraine and measures taken in response thereto. In the past, the failure, bankruptcy, or sale of various financial and other institutions created similar turmoil and uncertainty in such markets and industries. It is possible that a crisis in the global credit markets, the U.S. capital markets, the financial services industry or the U.S. economy may adversely affect our business, vendors and prospects, as well as our liquidity and financial condition. More specifically, our insurance carriers and insurance policies covering all aspects of our business may become financially unstable or may not be sufficient to cover any or all of our losses and may not continue to be available to us on acceptable terms, or at all. In addition, due to the rapidly rising inflation rate, we may experience increased costs of goods and services for our business.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A variety of risks associated with operating our business and marketing our medicines internationally could adversely affect our business. In addition to our U.S. operations, we are commercializing TEGSEDI in the EU, Canada, Latin America and certain Caribbean countries, and WAYLIVRA in the EU, Latin America and certain Caribbean countries. We face risks associated with our international operations, including possible unfavorable regulatory, pricing and reimbursement, political, tax and labor conditions, which could harm our business. Because we have international operations, we are subject to numerous risks associated with international business activities, including:</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">compliance with differing or unexpected regulatory requirements for our medicines and foreign employees;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">complexities associated with managing multiple payer reimbursement regimes, government payers or patient self-pay systems;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">difficulties in staffing and managing foreign operations;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in certain circumstances, increased dependence on the commercialization efforts and regulatory compliance of third-party distributors or strategic partners;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">foreign government taxes, regulations and permit requirements;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">U.S. and foreign government tariffs, trade restrictions, price and exchange controls and other regulatory requirements;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">anti-corruption laws, including the Foreign Corrupt Practices Act, or the FCPA, and its equivalent in foreign jurisdictions;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">economic weakness, including inflation, natural disasters, war, events of terrorism, political instability or public health issues or pandemics, such as the COVID-19 pandemic, in particular foreign countries or globally;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">fluctuations in currency exchange rates, which could result in increased operating expenses and reduced revenue, and other obligations related to doing business in another country;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">compliance with tax, employment, privacy, immigration and labor laws, regulations and restrictions for employees living or traveling abroad;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">workforce uncertainty in countries where labor unrest is more common than in the U.S.; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">changes in diplomatic and trade relationships.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The United Kingdom&#8217;s exit from the E.U. could increase these risks.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our business activities outside of the U.S. are subject to the FCPA and similar anti-bribery or anti-corruption laws, regulations or rules of other countries in which we operate, including the United Kingdom&#8217;s Bribery Act 2010. In many other countries, the healthcare providers who prescribe pharmaceuticals are employed by their government, and the purchasers of pharmaceuticals are government entities; therefore, any dealings with these prescribers and purchasers may be subject to regulation under the FCPA. There is no certainty that all employees and third-party business partners (including our distributors, wholesalers, agents, contractors and other partners) will comply with anti-bribery laws. In particular, we do not control the actions of manufacturers and other third-party agents, although we may be liable for their actions. Violation of these laws may result in civil or criminal sanctions, which could include monetary fines, criminal penalties, and disgorgement of past profits, which could have an adverse impact on our business and financial condition.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">The impact on us of the vote by the United Kingdom to leave the European Union cannot be predicted.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The withdrawal of the UK from the EU, commonly referred to as &#8220;Brexit,&#8221; may adversely impact our ability to obtain regulatory approvals of our medicines in the EU, result in restrictions or imposition of taxes and duties for importing our medicines into the EU, and may require us to incur additional expenses in order to develop, manufacture and commercialize our medicines in the EU.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Following the result of a referendum in 2016, the UK left the EU on January 31, 2020. Pursuant to the formal withdrawal arrangements agreed between the UK and the EU, the UK was subject to a transition period that ended December 31, 2020, or the Transition Period, during which EU rules continued to apply. A trade and cooperation agreement, or the Trade and Cooperation Agreement, that outlines the future trading relationship between the UK and the EU was signed in December 2020.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Since a significant proportion of the regulatory framework in the UK applicable to our business and our medicines is derived from EU directives and regulations, Brexit has had, and may continue to have, a material impact upon the regulatory regime with respect to the development, manufacture, importation, approval and commercialization of our medicines in the UK or the EU. For example, Great Britain is no longer covered by the centralized procedures for obtaining EU-wide marketing authorization from the EMA, and a separate marketing authorization will be required to market our medicines in Great Britain. It is currently unclear whether the Medicines &amp; Healthcare products Regulatory Agency in the UK is sufficiently prepared to handle the increased volume of marketing authorization applications that it is likely to receive. Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result of Brexit or otherwise, would delay or prevent us from commercializing our medicines in the UK or the EU</span>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">While the Trade and Cooperation Agreement provides for the tariff-free trade of medicinal products between the UK and the EU, there may be additional non-tariff costs to such trade which did not exist prior to the end of the Transition Period. Further, should the UK diverge from the EU from a regulatory perspective in relation to medicinal products, tariffs could be put into place in the future. We could therefore, both now and in the future, face significant additional expenses (when compared to the position prior to the end of the Transition Period) to operate our business</span>.</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS</div></td>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">DEFAULT UPON SENIOR SECURITIES</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">MINE SAFETY DISCLOSURES</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">OTHER INFORMATION</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
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<div style="text-align: left;"><a id="ITEM6"><!--Anchor--></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 6.</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 72pt" class="TRGRRTFtoHTMLTab">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">EXHIBITS</span></div>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a.</td>
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    <td style="width: 1.5%; vertical-align: top;">&#160;</td>
    <td style="width: 90.04%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Document</div></td>
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    <td style="width: 8.46%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="ex10-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.1</a></div></td>
    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment No. 2 dated July 28, 2022 to the Collaboration and License Agreement by and between the Registrant and BicycleTx Limited dated July 9, 2021. Portions of this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.</div></td>
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    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 8.46%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="ex31-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.1</a></div></td>
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    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 8.46%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="ex32-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32.1</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</span></div></td>
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    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certification Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.</div></td>
  </tr>
  <tr>
    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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<div><br /></div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="SIGNATURES"><!--Anchor--></a>SIGNATURES</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the Registrant and in the capacities and on the dates indicated.</div>
<div><br /></div>
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    <td style="width: 2.19%; vertical-align: bottom;">&#160;</td>
    <td style="width: 50.36%; vertical-align: top;">&#160;</td>
    <td style="width: 2.15%; vertical-align: bottom;">&#160;</td>
    <td style="width: 17.72%; vertical-align: top;">&#160;</td>
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    <td style="width: 27.57%; vertical-align: top;">&#160;</td>
    <td style="width: 2.19%; vertical-align: bottom;">&#160;</td>
    <td style="width: 50.36%; vertical-align: top;">&#160;</td>
    <td style="width: 2.15%; vertical-align: bottom;">&#160;</td>
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<DOCUMENT>
<TYPE>EX-10.1
<SEQUENCE>2
<FILENAME>ex10-1.htm
<DESCRIPTION>EXHIBIT 10.1
<TEXT>
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  <div style="text-align: right;"><font style="font-weight: bold;">Exhibit 10.1</font><br>
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  <div style="text-align: right;"><font style="font-weight: bold;"> <br>
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    </div>
    <div style="text-align: left;">Portions of this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.</div>
    <div>&#160;</div>
    <div style="text-align: left; text-indent: 36.8pt; margin-right: 51.65pt; margin-left: 11pt; font-weight: bold;">AMENDMENT NO. 2 TO COLLABORATION AND LICENSE AGREEMENT</div>
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    <div style="text-align: left; font-weight: bold; margin-left: 9pt;">&#160;THIS AMENDMENT NO. 2 TO COLLABORATION AND LICENSE AGREEMENT&#160; </div>
    <div style="text-align: left; margin-right: 40.8pt; margin-left: 11pt;">(&#8220;<font style="font-weight: bold;">Second Amendment</font>&#8221;) is made and entered into effective as of July 28, 2022 (&#8220;<font style="font-weight: bold;">Second Amendment Effective
        Date</font>&#8221;) by and between <font style="font-weight: bold;">BicycleTx Limited</font>, a company incorporated in England and Wales with a place of business at Blocks A &amp; B Portway Building, Granta Park, Great Abington, Cambridge, CB21 6GS (&#8220;<font style="font-weight: bold;">BicycleTx</font>&#8221;), and Ionis Pharmaceuticals, Inc., a Delaware corporation with a principal place of business at 2855 Gazelle Court, Carlsbad, California 92010, USA (&#8220;<font style="font-weight: bold;">Ionis</font>&#8221;).</div>
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    <div style="text-align: left; margin-left: 11pt;">BicycleTx and Ionis are referred to herein individually as a &#8220;<font style="font-weight: bold;">Party</font>&#8221; and collectively as the &#8220;<font style="font-weight: bold;">Parties</font>&#8221;.</div>
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    <div style="text-align: center; margin-right: 163pt; margin-left: 136.25pt; font-weight: bold;">BACKGROUND</div>
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    <div style="text-align: left; margin-right: 40.8pt; margin-left: 11pt;"><font style="font-weight: bold;">WHEREAS</font>, BicycleTx and Ionis entered into that certain Collaboration and License Agreement dated as of July 9, 2021, as amended (the &#8220;<font style="font-weight: bold;">Agreement</font>&#8221;), pursuant to which the Parties agreed to collaborate in the research and development of products incorporating TfR1 Bicycles directed against certain Targets;</div>
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    <div style="text-align: left; margin-right: 51.65pt; margin-left: 11pt;"><font style="font-weight: bold;">WHEREAS </font>the Parties amended the Agreement by the First Amendment effective as of 17 December 2021 to enable the Parties to conduct certain
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    <div style="text-align: left; margin-right: 40.8pt; margin-left: 11pt;"><font style="font-weight: bold;">WHEREAS</font>, the Parties now seek to further amend the Agreement to extend the Additional Research Period and the Initial Period; and</div>
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    <div style="text-align: left; margin-right: 16.1pt; margin-left: 11pt;"><font style="font-weight: bold;">WHEREAS</font>, Section 12.3 of the Agreement provides that the Agreement may only be modified by a written instrument duly executed by authorized
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    <div style="text-align: left; margin-right: 51.65pt; margin-left: 11pt;"><font style="font-weight: bold;">NOW, THEREFORE</font>, the Parties desire, for good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, to
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    <div style="text-align: center; text-indent: -0.15pt; margin-right: 227.1pt; margin-left: 200.25pt; font-weight: bold;">ARTICLE 1 </div>
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            <div><font style="font-weight: bold;">Capitalized Terms. </font>Capitalized terms used in this Second Amendment shall have the meanings set forth in the Agreement and First Amendment, unless otherwise defined in this Second Amendment. Section
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            <div><font style="font-weight: bold;">Additional Activities</font>. The Parties desire to extend the Additional Research Period by [***]. Accordingly, Section 2.1 of Article 2 of the First Amendment shall be deleted in its entirety and replaced
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    <div style="text-align: left; margin-right: 16.1pt; margin-left: 47pt;">&#8220;<font style="font-style: italic;">BicycleTx will perform the research activities set forth on Schedule 1 attached hereto (the &#8220;</font><font style="font-weight: bold; font-style: italic;">Additional Activities</font><font style="font-style: italic;">&#8221;) during the period beginning on [</font>***<font style="font-style: italic;">] and continuing for</font></div>
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    <div style="text-align: left; margin-right: 51.65pt; margin-left: 47pt;"><font style="font-style: italic;">[</font>***<font style="font-style: italic;">] from such date (the &#8220;</font><font style="font-weight: bold; font-style: italic;">Additional
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            <div><font style="font-weight: bold;">Initial Period. </font>The Parties wish to extend the Initial Period by three months. Accordingly, Section 2.4.1 of Article 2 of the First Amendment shall be deleted in its entirety and replaced with:</div>
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    <div>&#160;</div>
    <div style="text-align: left; margin-right: 40.8pt; margin-left: 47pt;">&#8220;<font style="font-style: italic;">2.4.1 </font><font style="font-weight: bold; font-style: italic;">Determination of Success Criteria and Initial Data Package</font><font style="font-style: italic;">. During the first [</font>***<font style="font-style: italic;">] period of the Additional Research Period (the &#8220;</font><font style="font-weight: bold; font-style: italic;">Initial Period</font><font style="font-style: italic;">&#8221;), the Parties, through the JSC, shall discuss in good faith and mutually agree upon (a) the success criteria by which the Parties will determine whether the initial goals of the Additional Activities have been achieved, and whether the
        Parties should continue to perform such Additional Activities for the remainder of the Additional Research Period (the &#8220;</font><font style="font-weight: bold; font-style: italic;">Success Criteria</font><font style="font-style: italic;">&#8221;) and (b)
        the nature and scope of the data generated by BicycleTx in the course of performing the Additional Activities during the Initial Period, which data BicycleTx will deliver to the JSC pursuant to Section 2.4.2 (the &#8220;</font><font style="font-weight: bold; font-style: italic;">Initial Data Package</font><font style="font-style: italic;">&#8221;).</font>&#8221;</div>
    <div>&#160;</div>
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    <div style="text-align: center; text-indent: -0.15pt; margin-right: 215.2pt; margin-left: 188.4pt; font-weight: bold;">MISCELLANEOUS</div>
    <div style="text-align: center; text-indent: -0.15pt; margin-right: 215.2pt; margin-left: 188.4pt; font-weight: bold;"> <br>
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        <tr>
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          </td>
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          <td style="width: auto; vertical-align: top;">
            <div><font style="font-weight: bold;">No Waiver</font>. Nothing in this Second Amendment is intended to operate as a waiver of any claims either Party may have against the other Party arising prior to the date of this Second Amendment under the
              Agreement. Any term or condition of this Second Amendment may be waived at any time by the Party that is entitled to the benefit thereof, but no such waiver shall be effective unless it is in writing and signed by the Party waiving such term
              or condition. The waiver by either Party hereto of any right hereunder or of a breach by the other Party shall not be deemed a waiver of any other right hereunder or of any other breach by such other Party whether of a similar nature or
              otherwise.</div>
          </td>
        </tr>

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    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbd374f929fae4f8a919ec69725a7f42c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

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          </td>
          <td style="width: 22.2pt; vertical-align: top;">3.2</td>
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            <div><font style="font-weight: bold;">Miscellaneous. </font>This Second Amendment and the performance, enforcement, breach, and termination hereof shall be interpreted, governed by, and construed in accordance with the laws of the State of New
              York, United States excluding any conflicts or choice of law rule or principle that might otherwise refer construction or interpretation of this Second Amendment to the substantive law of another jurisdiction. Any dispute arising from or
              relating to this Second Amendment will be subject to resolution in accordance with Section 12.2 of the Agreement. Except as specifically amended by this Second Amendment, the terms and conditions of the Agreement (as amended by the First
              Amendment) shall remain in full force and effect. Except to the extent expressly provided herein, the Agreement, as amended by the First Amendment and this Second Amendment, including all appendices, exhibits and schedules to each of the
              foregoing, sets forth the entire agreement and understanding between the Parties with respect to the subject matter of the Agreement (as amended) and all prior agreements, understandings, promises, and representations, whether written or
              oral, with respect thereto are superseded hereby. This Second Amendment may be executed in two or more counterparts in original, facsimile, PDF, or other electronic format, each of which shall be an original, and all of which together shall
              constitute one instrument.</div>
          </td>
        </tr>

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    <div>&#160;</div>
    <div style="text-align: center; margin-right: 163.15pt; margin-left: 136.25pt;">[Remainder of Page Intentionally Left Blank]</div>
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              <tr>
                <td style="width: 50%;">
                  <div style="text-align: left; margin-left: 1pt; font-weight: bold;">CONFIDENTIAL</div>
                </td>
                <td style="width: 50%;">
                  <div style="text-align: right; margin-left: 1pt; font-style: italic; font-weight: bold;">Execution Version</div>
                </td>
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    <div>
      <div style="text-align: left; margin-left: 2.5pt;"><font style="font-weight: bold;">THIS AMENDMENT NO. 2 TO COLLABORATION AND LICENSE AGREEMENT </font>is executed by the authorized representatives of the Parties as of the Second Amendment Effective
        Date.</div>
      <div style="text-align: left; margin-left: 2.5pt;">&#160;</div>
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            <div style="margin-left: 2.5pt; font-weight: bold;">BICYCLETX LIMITED</div>
          </td>
          <td style="width: 50%; vertical-align: top;">
            <div style="font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1"><br>
          </td>
          <td style="width: 50%; vertical-align: top;" rowspan="1"><br>
          </td>
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    <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

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          <td style="width: 4%; vertical-align: top;">
            <div style="margin-left: 2.5pt;">By<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">:</sub> <br>
            </div>
          </td>
          <td style="width: 46%; vertical-align: top;">/s/ Michael Skynner</td>
          <td style="width: 4%; vertical-align: top;">
            <div>By<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">:</sub></div>
          </td>
          <td style="width: 46%; vertical-align: top;"> /s/ Brett Monia</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" rowspan="1" colspan="2"><br>
          </td>
          <td style="vertical-align: top;" rowspan="1" colspan="2"><br>
          </td>
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          <td style="width: 4%; vertical-align: top;">
            <div style="margin-left: 2.5pt;">Name: <br>
            </div>
          </td>
          <td style="width: 46%; vertical-align: top;">Michael Skynner</td>
          <td style="width: 4%; vertical-align: top;">
            <div>Name: <br>
            </div>
          </td>
          <td style="width: 46%; vertical-align: top;">Brett Monia</td>
        </tr>

    </table>
    <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

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          <td style="width: 4%; vertical-align: top;">
            <div style="margin-left: 2.5pt;">Title: <br>
            </div>
          </td>
          <td style="width: 46%; vertical-align: top;">Chief Technology Officer</td>
          <td style="width: 4%; vertical-align: top;">
            <div>Title: <br>
            </div>
          </td>
          <td style="width: 46%; vertical-align: top;">CEO</td>
        </tr>

    </table>
    <div>&#160;</div>
    <div> <br>
    </div>
  </div>
  <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">3</font>
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<DOCUMENT>
<TYPE>EX-31.1
<SEQUENCE>3
<FILENAME>ex31-1.htm
<DESCRIPTION>EXHIBIT 31.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals
         Document created using Broadridge PROfile 22.9.1.5075
         Copyright 1995 - 2022 Broadridge -->
  </head><body style="font-family: 'Times New Roman'; font-size: 10pt;"><div id="TRGRSegment:956881ca-11d1-4726-85b7-68a37548513a"><div style="text-align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;"><font style="font-size: 12pt; font-family: 'Times New Roman';"><hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center"></font>EXHIBIT 31.1</div><div><br></div><div style="text-align: center; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">I, Brett P. Monia, certify that:</div><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc4b2e53a68844552b5d4cfe56b986156"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">1.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">I have reviewed this Quarterly Report on Form 10-Q of Ionis Pharmaceuticals, Inc.;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z9e11bb8625504e0ca92cf7aa9a4b8ca6"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">2.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Based on my knowledge, this quarterly report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this quarterly report;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc077dace4768429db2cc608fc1b6dbb0"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">3.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Based on my knowledge, the condensed consolidated financial statements, and other financial information included in this quarterly report, fairly present in all material respects the financial condition, condensed consolidated results of operations and condensed consolidated cash flows of the registrant as of, and for, the periods presented in this quarterly report;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zd1ee6913412949a4a07bb008c190ed29"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">4.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">The registrant&#8217;s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc22624a5432a4bcfa4fb702182f9649c"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">a)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z2e733ab924684bdc89d50b6d6ca709e2"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">b)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zbba1e32c1c814e4ca07b32c75344dac5"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">c)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Evaluated the effectiveness of the registrant&#8217;s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z3cb17557170144e8af718b2bf99cb0d5"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">d)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Disclosed in this report any change in the registrant&#8217;s internal control over financial reporting that occurred during the registrant&#8217;s most recent fiscal quarter (the registrant&#8217;s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant&#8217;s internal control over financial reporting; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zcfba188527ee490595b7960603d1dd3a"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">5.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">The registrant&#8217;s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant&#8217;s auditors and the audit committee of registrant&#8217;s board of directors (or persons performing the equivalent functions):</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z9d41cd4a46ca445684c5c1cc40d60248"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">a)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant&#8217;s ability to record, process, summarize and report financial information; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="ze2776795e4cd4b1da09b41291955d171"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">b)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant&#8217;s internal control over financial reporting.</div></td></tr></table><div style="text-align: justify; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zaf7bbf4ece22420bb5587fc3c9960bd4"><tr><td style="width: 27.59%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Dated: November 9, 2022</div></td><td style="width: 72.41%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.59%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td><td style="width: 72.41%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.59%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">/s/ BRETT P. MONIA</div></td><td style="width: 72.41%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.59%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Brett P. Monia, Ph.D.</div></td><td style="width: 72.41%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.59%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Chief Executive Officer</div></td><td style="width: 72.41%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr></table><div><br></div><div style="text-align: justify; font-family: 'Times New Roman'; font-size: 12pt;"><hr style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center"></div></div></body></html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-31.2
<SEQUENCE>4
<FILENAME>ex31-2.htm
<DESCRIPTION>EXHIBIT 31.2
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals
         Document created using Broadridge PROfile 22.9.1.5075
         Copyright 1995 - 2022 Broadridge -->
  </head><body style="font-family: 'Times New Roman'; font-size: 10pt;"><div id="TRGRSegment:9770b480-fdae-48ad-8dab-7c414e81bcac"><div style="text-align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;"><font style="font-size: 12pt; font-family: 'Times New Roman';"><hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center"></font>EXHIBIT 31.2</div><div><br></div><div style="text-align: center; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">I, Elizabeth L. Hougen, certify that:</div><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z1dc40ee1c31e4c3692c9d165b0d5d732"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">1.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">I have reviewed this Quarterly Report on Form 10-Q of Ionis Pharmaceuticals, Inc.;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc2ea75e5bbc349288cdea4a0f0d075f1"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">2.</td><td style="width: auto; 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<TYPE>EX-101.LAB
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<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesCurrentAbstract" xlink:to="us-gaap_AccruedLiabilitiesCurrentAbstract_lbl" xlink:title="label: AccruedLiabilitiesCurrentAbstract to us-gaap_AccruedLiabilitiesCurrentAbstract_lbl" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdditionalPaidInCapitalCommonStock" xlink:label="AdditionalPaidInCapitalCommonStock" xlink:title="AdditionalPaidInCapitalCommonStock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdditionalPaidInCapitalCommonStock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AdditionalPaidInCapitalCommonStock_lbl" xml:lang="en-US" id="us-gaap_AdditionalPaidInCapitalCommonStock_lbl">Additional paid-in capital</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AdditionalPaidInCapitalCommonStock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AdditionalPaidInCapitalCommonStock_lbl1" xml:lang="en-US" id="us-gaap_AdditionalPaidInCapitalCommonStock_lbl1">Additional Paid in Capital, Common Stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdditionalPaidInCapitalCommonStock" xlink:to="us-gaap_AdditionalPaidInCapitalCommonStock_lbl1" xlink:title="label: AdditionalPaidInCapitalCommonStock to us-gaap_AdditionalPaidInCapitalCommonStock_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued_lbl" xml:lang="en-US" id="us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued_lbl">Issuance of warrants</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdjustmentsToAdditionalPaidInCapitalWarrantIssued" xlink:to="us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued_lbl1" xlink:title="label: AdjustmentsToAdditionalPaidInCapitalWarrantIssued to us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalOther" xlink:label="AdjustmentsToAdditionalPaidInCapitalOther" xlink:title="AdjustmentsToAdditionalPaidInCapitalOther" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalOther_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AdjustmentsToAdditionalPaidInCapitalOther_lbl" xml:lang="en-US" id="us-gaap_AdjustmentsToAdditionalPaidInCapitalOther_lbl">Purchase of note hedges</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalOther_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AdjustmentsToAdditionalPaidInCapitalOther_lbl1" xml:lang="en-US" id="us-gaap_AdjustmentsToAdditionalPaidInCapitalOther_lbl1">Adjustments to Additional Paid in Capital, Other</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:label="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:title="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:label="AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="AllocatedShareBasedCompensationExpense" xlink:title="AllocatedShareBasedCompensationExpense" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AmortizationOfIntangibleAssets" xlink:label="AmortizationOfIntangibleAssets" xlink:title="AmortizationOfIntangibleAssets" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfIntangibleAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfIntangibleAssets_lbl1" xml:lang="en-US" id="us-gaap_AmortizationOfIntangibleAssets_lbl1">Amortization of Intangible Assets</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfFinancingCosts_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfFinancingCosts_lbl1" xml:lang="en-US" id="us-gaap_AmortizationOfFinancingCosts_lbl1">Amortization of Debt Issuance Costs</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="AssetsFairValueDisclosure" xlink:title="AssetsFairValueDisclosure" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_Assets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Assets_lbl1" xml:lang="en-US" id="us-gaap_Assets_lbl1">Assets</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsCurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AssetsCurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_AssetsCurrentAbstract_lbl1">Assets, Current [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:title="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl1">Debt Securities, Available-for-Sale, Accumulated Gross Unrealized Loss, before Tax</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:label="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:title="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl">Available-for-sale Securities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl" xlink:title="label: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl1">Debt Securities, Available-for-Sale, Fair Value to Amortized Cost, after Allowance for Credit Loss [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl">Unrealized Losses [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl1">Debt Securities, Available-for-Sale, Unrealized Loss Position, Accumulated Loss [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAbstract" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_lbl" xlink:title="label: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl">Collaborative Arrangements and Licensing Agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementDisclosureTextBlock" xlink:to="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl" xlink:title="label: CollaborativeArrangementDisclosureTextBlock to us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1">Collaborative Arrangement Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementDisclosureTextBlock" xlink:to="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" xlink:title="label: CollaborativeArrangementDisclosureTextBlock to us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommitmentsAndContingenciesDisclosureAbstract" xlink:label="CommitmentsAndContingenciesDisclosureAbstract" xlink:title="CommitmentsAndContingenciesDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommitmentsAndContingenciesDisclosureAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommitmentsAndContingenciesDisclosureAbstract_lbl" xml:lang="en-US" id="us-gaap_CommitmentsAndContingenciesDisclosureAbstract_lbl">Legal Proceedings [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommitmentsAndContingenciesDisclosureAbstract" xlink:to="us-gaap_CommitmentsAndContingenciesDisclosureAbstract_lbl" xlink:title="label: CommitmentsAndContingenciesDisclosureAbstract to us-gaap_CommitmentsAndContingenciesDisclosureAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommonStockMember" xlink:label="CommonStockMember" xlink:title="CommonStockMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockMember_lbl" xml:lang="en-US" id="us-gaap_CommonStockMember_lbl">Common Stock [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockMember" xlink:to="us-gaap_CommonStockMember_lbl" xlink:title="label: CommonStockMember to us-gaap_CommonStockMember_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockParOrStatedValuePerShare_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockParOrStatedValuePerShare_lbl" xml:lang="en-US" id="us-gaap_CommonStockParOrStatedValuePerShare_lbl">Common stock, par value (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockParOrStatedValuePerShare" xlink:to="us-gaap_CommonStockParOrStatedValuePerShare_lbl" xlink:title="label: CommonStockParOrStatedValuePerShare to us-gaap_CommonStockParOrStatedValuePerShare_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockParOrStatedValuePerShare_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockParOrStatedValuePerShare_lbl1" xml:lang="en-US" id="us-gaap_CommonStockParOrStatedValuePerShare_lbl1">Common Stock, Par or Stated Value Per Share</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockParOrStatedValuePerShare" xlink:to="us-gaap_CommonStockParOrStatedValuePerShare_lbl1" xlink:title="label: CommonStockParOrStatedValuePerShare to us-gaap_CommonStockParOrStatedValuePerShare_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommonStockValue" xlink:label="CommonStockValue" xlink:title="CommonStockValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockValue_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_CommonStockValue_lbl" xml:lang="en-US" id="us-gaap_CommonStockValue_lbl">Common stock, $0.001 par value; 300,000,000 shares authorized, 142,017,411 and 141,210,015 shares issued and outstanding at September 30, 2022 (unaudited) and December 31, 2021, respectively</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockValue" xlink:to="us-gaap_CommonStockValue_lbl" xlink:title="label: CommonStockValue to us-gaap_CommonStockValue_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockValue_lbl1" xml:lang="en-US" id="us-gaap_CommonStockValue_lbl1">Common Stock, Value, Issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockValue" xlink:to="us-gaap_CommonStockValue_lbl1" xlink:title="label: CommonStockValue to us-gaap_CommonStockValue_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesIssued_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockSharesIssued_lbl" xml:lang="en-US" id="us-gaap_CommonStockSharesIssued_lbl">Common stock, shares issued (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesIssued" xlink:to="us-gaap_CommonStockSharesIssued_lbl" xlink:title="label: CommonStockSharesIssued to us-gaap_CommonStockSharesIssued_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesIssued_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockSharesIssued_lbl1" xml:lang="en-US" id="us-gaap_CommonStockSharesIssued_lbl1">Common Stock, Shares, Issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesIssued" xlink:to="us-gaap_CommonStockSharesIssued_lbl1" xlink:title="label: CommonStockSharesIssued to us-gaap_CommonStockSharesIssued_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommonStockSharesAuthorized" xlink:label="CommonStockSharesAuthorized" xlink:title="CommonStockSharesAuthorized" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesAuthorized_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockSharesAuthorized_lbl" xml:lang="en-US" id="us-gaap_CommonStockSharesAuthorized_lbl">Common stock, shares authorized (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesAuthorized" xlink:to="us-gaap_CommonStockSharesAuthorized_lbl" xlink:title="label: CommonStockSharesAuthorized to us-gaap_CommonStockSharesAuthorized_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesAuthorized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockSharesAuthorized_lbl1" xml:lang="en-US" id="us-gaap_CommonStockSharesAuthorized_lbl1">Common Stock, Shares Authorized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesAuthorized" xlink:to="us-gaap_CommonStockSharesAuthorized_lbl1" xlink:title="label: CommonStockSharesAuthorized to us-gaap_CommonStockSharesAuthorized_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommonStockSharesOutstanding" xlink:label="CommonStockSharesOutstanding" xlink:title="CommonStockSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesOutstanding_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockSharesOutstanding_lbl" xml:lang="en-US" id="us-gaap_CommonStockSharesOutstanding_lbl">Common stock, shares outstanding (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesOutstanding" xlink:to="us-gaap_CommonStockSharesOutstanding_lbl" xlink:title="label: CommonStockSharesOutstanding to us-gaap_CommonStockSharesOutstanding_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesOutstanding_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockSharesOutstanding_lbl1" xml:lang="en-US" id="us-gaap_CommonStockSharesOutstanding_lbl1">Common Stock, Shares, Outstanding</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesOutstanding" xlink:to="us-gaap_CommonStockSharesOutstanding_lbl1" xlink:title="label: CommonStockSharesOutstanding to us-gaap_CommonStockSharesOutstanding_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="ComprehensiveIncomeNetOfTax" xlink:title="ComprehensiveIncomeNetOfTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_ComprehensiveIncomeNetOfTax_lbl" xml:lang="en-US" id="us-gaap_ComprehensiveIncomeNetOfTax_lbl">Comprehensive loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_ComprehensiveIncomeNetOfTax_lbl" xlink:title="label: ComprehensiveIncomeNetOfTax to us-gaap_ComprehensiveIncomeNetOfTax_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ComprehensiveIncomeNetOfTax_lbl1" xml:lang="en-US" id="us-gaap_ComprehensiveIncomeNetOfTax_lbl1">Comprehensive Income (Loss), Net of Tax, Attributable to Parent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_ComprehensiveIncomeNetOfTax_lbl1" xlink:title="label: ComprehensiveIncomeNetOfTax to us-gaap_ComprehensiveIncomeNetOfTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="ConcentrationRiskByTypeAxis" xlink:title="ConcentrationRiskByTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskByTypeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskByTypeAxis_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskByTypeAxis_lbl">Concentration Risk Type [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskByTypeAxis" xlink:to="us-gaap_ConcentrationRiskByTypeAxis_lbl" xlink:title="label: ConcentrationRiskByTypeAxis to us-gaap_ConcentrationRiskByTypeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain" xlink:title="ConcentrationRiskTypeDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskTypeDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskTypeDomain_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskTypeDomain_lbl">Concentration Risk Type [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskTypeDomain" xlink:to="us-gaap_ConcentrationRiskTypeDomain_lbl" xlink:title="label: ConcentrationRiskTypeDomain to us-gaap_ConcentrationRiskTypeDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskBenchmarkDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskBenchmarkDomain_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskBenchmarkDomain_lbl">Concentration Risk Benchmark [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskBenchmarkDomain" xlink:to="us-gaap_ConcentrationRiskBenchmarkDomain_lbl" xlink:title="label: ConcentrationRiskBenchmarkDomain to us-gaap_ConcentrationRiskBenchmarkDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConcentrationRiskPercentage1" xlink:label="ConcentrationRiskPercentage1" xlink:title="ConcentrationRiskPercentage1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskPercentage1_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskPercentage1_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskPercentage1_lbl">Concentration percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskPercentage1" xlink:to="us-gaap_ConcentrationRiskPercentage1_lbl" xlink:title="label: ConcentrationRiskPercentage1 to us-gaap_ConcentrationRiskPercentage1_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="ConcentrationRiskByBenchmarkAxis" xlink:title="ConcentrationRiskByBenchmarkAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskByBenchmarkAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskByBenchmarkAxis_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskByBenchmarkAxis_lbl">Concentration Risk Benchmark [Axis]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConsolidationPolicyTextBlock" xlink:label="ConsolidationPolicyTextBlock" xlink:title="ConsolidationPolicyTextBlock" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl">Current portion of deferred contract revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1">Contract with Customer, Liability, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiabilityAbstract" xlink:label="ContractWithCustomerLiabilityAbstract" xlink:title="ContractWithCustomerLiabilityAbstract" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityAbstract" xlink:to="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" xlink:title="label: ContractWithCustomerLiabilityAbstract to us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiability_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability_lbl">Deferred revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiability" xlink:to="us-gaap_ContractWithCustomerLiability_lbl" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiability_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability_lbl1">Contract with Customer, Liability</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiability" xlink:to="us-gaap_ContractWithCustomerLiability_lbl1" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerAssetNetCurrent" xlink:label="ContractWithCustomerAssetNetCurrent" xlink:title="ContractWithCustomerAssetNetCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerAssetNetCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerAssetNetCurrent_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerAssetNetCurrent_lbl">Contracts receivable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerAssetNetCurrent" xlink:to="us-gaap_ContractWithCustomerAssetNetCurrent_lbl" xlink:title="label: ContractWithCustomerAssetNetCurrent to us-gaap_ContractWithCustomerAssetNetCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1">Contract with Customer, Asset, after Allowance for Credit Loss, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerAssetNetCurrent" xlink:to="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" xlink:title="label: ContractWithCustomerAssetNetCurrent to us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="ContractWithCustomerLiabilityNoncurrent" xlink:title="ContractWithCustomerLiabilityNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl">Long-term deferred contract revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityNoncurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl" xlink:title="label: ContractWithCustomerLiabilityNoncurrent to us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1">Contract with Customer, Liability, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityNoncurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xlink:title="label: ContractWithCustomerLiabilityNoncurrent to us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized" xlink:label="ContractWithCustomerLiabilityRevenueRecognized" xlink:title="ContractWithCustomerLiabilityRevenueRecognized" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl">Revenue recognized from amounts in beginning deferred revenue balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityRevenueRecognized" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xlink:title="label: ContractWithCustomerLiabilityRevenueRecognized to us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1">Contract with Customer, Liability, Revenue Recognized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityRevenueRecognized" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xlink:title="label: ContractWithCustomerLiabilityRevenueRecognized to us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractReceivablesAbstract" xlink:label="ContractReceivablesAbstract" xlink:title="ContractReceivablesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractReceivablesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractReceivablesAbstract_lbl" xml:lang="en-US" id="us-gaap_ContractReceivablesAbstract_lbl">Contracts Receivable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractReceivablesAbstract" xlink:to="us-gaap_ContractReceivablesAbstract_lbl" xlink:title="label: ContractReceivablesAbstract to us-gaap_ContractReceivablesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractReceivablesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractReceivablesAbstract_lbl1" xml:lang="en-US" id="us-gaap_ContractReceivablesAbstract_lbl1">Contracts Receivable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractReceivablesAbstract" xlink:to="us-gaap_ContractReceivablesAbstract_lbl1" xlink:title="label: ContractReceivablesAbstract to us-gaap_ContractReceivablesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConvertibleDebtNoncurrent" xlink:label="ConvertibleDebtNoncurrent" xlink:title="ConvertibleDebtNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebtNoncurrent_lbl" xml:lang="en-US" id="us-gaap_ConvertibleDebtNoncurrent_lbl">Convertible senior notes, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent_lbl" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtNoncurrent_lbl1">Convertible Debt, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent_lbl1" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:label="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:title="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" xlink:title="label: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1">Convertible Notes Payable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" xlink:title="label: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConvertibleDebtTableTextBlock" xlink:label="ConvertibleDebtTableTextBlock" xlink:title="ConvertibleDebtTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebtTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ConvertibleDebtTableTextBlock_lbl">Convertible Senior Notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtTableTextBlock" xlink:to="us-gaap_ConvertibleDebtTableTextBlock_lbl" xlink:title="label: ConvertibleDebtTableTextBlock to us-gaap_ConvertibleDebtTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtTableTextBlock_lbl1">Convertible Debt [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtTableTextBlock" xlink:to="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xlink:title="label: ConvertibleDebtTableTextBlock to us-gaap_ConvertibleDebtTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="CorporateDebtSecuritiesMember" xlink:title="CorporateDebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CorporateDebtSecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CorporateDebtSecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_CorporateDebtSecuritiesMember_lbl">Corporate Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CorporateDebtSecuritiesMember" xlink:to="us-gaap_CorporateDebtSecuritiesMember_lbl" xlink:title="label: CorporateDebtSecuritiesMember to us-gaap_CorporateDebtSecuritiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CorporateDebtSecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CorporateDebtSecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_CorporateDebtSecuritiesMember_lbl1">Corporate Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CorporateDebtSecuritiesMember" xlink:to="us-gaap_CorporateDebtSecuritiesMember_lbl1" xlink:title="label: CorporateDebtSecuritiesMember to us-gaap_CorporateDebtSecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="CostOfGoodsAndServicesSold" xlink:title="CostOfGoodsAndServicesSold" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSold_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfGoodsAndServicesSold_lbl" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSold_lbl">Cost of sales</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSold" xlink:to="us-gaap_CostOfGoodsAndServicesSold_lbl" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSold_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfGoodsAndServicesSold_lbl1" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSold_lbl1">Cost of Goods and Services Sold</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSold" xlink:to="us-gaap_CostOfGoodsAndServicesSold_lbl1" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostOfSalesPolicyTextBlock" xlink:label="CostOfSalesPolicyTextBlock" xlink:title="CostOfSalesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfSalesPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_CostOfSalesPolicyTextBlock_lbl">Cost of Sales</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesPolicyTextBlock" xlink:to="us-gaap_CostOfSalesPolicyTextBlock_lbl" xlink:title="label: CostOfSalesPolicyTextBlock to us-gaap_CostOfSalesPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_CostOfSalesPolicyTextBlock_lbl1">Cost of Goods and Service [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesPolicyTextBlock" xlink:to="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xlink:title="label: CostOfSalesPolicyTextBlock to us-gaap_CostOfSalesPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostOfSalesMember" xlink:label="CostOfSalesMember" xlink:title="CostOfSalesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfSalesMember_lbl" xml:lang="en-US" id="us-gaap_CostOfSalesMember_lbl">Cost of Sales [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesMember" xlink:to="us-gaap_CostOfSalesMember_lbl" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfSalesMember_lbl1" xml:lang="en-US" id="us-gaap_CostOfSalesMember_lbl1">Cost of Sales [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesMember" xlink:to="us-gaap_CostOfSalesMember_lbl1" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="CostsAndExpensesAbstract" xlink:title="CostsAndExpensesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl">Expenses:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpensesAbstract_lbl" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl1">Costs and Expenses [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostsAndExpenses" xlink:label="CostsAndExpenses" xlink:title="CostsAndExpenses" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_CostsAndExpenses_lbl" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl">Total operating expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpenses_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl1">Costs and Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl1" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CreditConcentrationRiskMember" xlink:label="CreditConcentrationRiskMember" xlink:title="CreditConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CreditConcentrationRiskMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CreditConcentrationRiskMember_lbl" xml:lang="en-US" id="us-gaap_CreditConcentrationRiskMember_lbl">Credit Concentration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CreditConcentrationRiskMember" xlink:to="us-gaap_CreditConcentrationRiskMember_lbl" xlink:title="label: CreditConcentrationRiskMember to us-gaap_CreditConcentrationRiskMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CustomerConcentrationRiskMember" xlink:label="CustomerConcentrationRiskMember" xlink:title="CustomerConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CustomerConcentrationRiskMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CustomerConcentrationRiskMember_lbl" xml:lang="en-US" id="us-gaap_CustomerConcentrationRiskMember_lbl">Strategic Partner [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_CustomerConcentrationRiskMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CustomerConcentrationRiskMember_lbl1" xml:lang="en-US" id="us-gaap_CustomerConcentrationRiskMember_lbl1">Customer Concentration Risk [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1">Debt Securities, Available-for-Sale, Continuous Unrealized Loss Position, 12 Months or Longer, Accumulated Loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss to us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtDisclosureAbstract" xlink:label="DebtDisclosureAbstract" xlink:title="DebtDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtDisclosureAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtDisclosureAbstract_lbl" xml:lang="en-US" id="us-gaap_DebtDisclosureAbstract_lbl">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtDisclosureAbstract" xlink:to="us-gaap_DebtDisclosureAbstract_lbl" xlink:title="label: DebtDisclosureAbstract to us-gaap_DebtDisclosureAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentRepurchasedFaceAmount" xlink:label="DebtInstrumentRepurchasedFaceAmount" xlink:title="DebtInstrumentRepurchasedFaceAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentRepurchasedFaceAmount_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentRepurchasedFaceAmount_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentRepurchasedFaceAmount_lbl">Principal amount repurchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentRepurchasedFaceAmount" xlink:to="us-gaap_DebtInstrumentRepurchasedFaceAmount_lbl" xlink:title="label: DebtInstrumentRepurchasedFaceAmount to us-gaap_DebtInstrumentRepurchasedFaceAmount_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1" xlink:label="DebtInstrumentConvertibleConversionPrice1" xlink:title="DebtInstrumentConvertibleConversionPrice1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl">Conversion price per share (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPrice1" xlink:to="us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl" xlink:title="label: DebtInstrumentConvertibleConversionPrice1 to us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentTable" xlink:label="DebtInstrumentTable" xlink:title="DebtInstrumentTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentTable_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentTable_lbl">Schedule of Long-term Debt Instruments [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentTable" xlink:to="us-gaap_DebtInstrumentTable_lbl" xlink:title="label: DebtInstrumentTable to us-gaap_DebtInstrumentTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtDisclosureTextBlock" xlink:label="DebtDisclosureTextBlock" xlink:title="DebtDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_DebtDisclosureTextBlock_lbl">Convertible Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtDisclosureTextBlock" xlink:to="us-gaap_DebtDisclosureTextBlock_lbl" xlink:title="label: DebtDisclosureTextBlock to us-gaap_DebtDisclosureTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_DebtDisclosureTextBlock_lbl1">Debt Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtDisclosureTextBlock" xlink:to="us-gaap_DebtDisclosureTextBlock_lbl1" xlink:title="label: DebtDisclosureTextBlock to us-gaap_DebtDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:label="DebtInstrumentCarryingAmount" xlink:title="DebtInstrumentCarryingAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentCarryingAmount_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentCarryingAmount_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentCarryingAmount_lbl">Outstanding principal balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentCarryingAmount" xlink:to="us-gaap_DebtInstrumentCarryingAmount_lbl" xlink:title="label: DebtInstrumentCarryingAmount to us-gaap_DebtInstrumentCarryingAmount_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentAxis_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentAxis_lbl">Debt Instrument [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentAxis_lbl" xlink:title="label: DebtInstrumentAxis to us-gaap_DebtInstrumentAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="DebtInstrumentLineItems" xlink:title="DebtInstrumentLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentLineItems_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentLineItems_lbl">Debt Instrument [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentLineItems_lbl" xlink:title="label: DebtInstrumentLineItems to us-gaap_DebtInstrumentLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="DebtInstrumentFaceAmount" xlink:title="DebtInstrumentFaceAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentFaceAmount_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_DebtInstrumentFaceAmount_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount_lbl">Face amount of offering</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentFaceAmount" xlink:to="us-gaap_DebtInstrumentFaceAmount_lbl" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentFaceAmount_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentFaceAmount_lbl1" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount_lbl1">Debt Instrument, Face Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentFaceAmount" xlink:to="us-gaap_DebtInstrumentFaceAmount_lbl1" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:label="DebtInstrumentInterestRateEffectivePercentage" xlink:title="DebtInstrumentInterestRateEffectivePercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl">Effective interest rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateEffectivePercentage" xlink:to="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl" xlink:title="label: DebtInstrumentInterestRateEffectivePercentage to us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1">Debt Instrument, Interest Rate, Effective Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateEffectivePercentage" xlink:to="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" xlink:title="label: DebtInstrumentInterestRateEffectivePercentage to us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl">Interest rate on convertible senior notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateStatedPercentage" xlink:to="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl" xlink:title="label: DebtInstrumentInterestRateStatedPercentage to us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1">Interest rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateStatedPercentage" xlink:to="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1" xlink:title="label: DebtInstrumentInterestRateStatedPercentage to us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentNameDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentNameDomain_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentNameDomain_lbl">Debt Instrument, Name [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNameDomain" xlink:to="us-gaap_DebtInstrumentNameDomain_lbl" xlink:title="label: DebtInstrumentNameDomain to us-gaap_DebtInstrumentNameDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentMaturityDate" xlink:label="DebtInstrumentMaturityDate" xlink:title="DebtInstrumentMaturityDate" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentMaturityDate_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentMaturityDate_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentMaturityDate_lbl">Maturity date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentMaturityDate" xlink:to="us-gaap_DebtInstrumentMaturityDate_lbl" xlink:title="label: DebtInstrumentMaturityDate to us-gaap_DebtInstrumentMaturityDate_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtPolicyTextBlock" xlink:label="DebtPolicyTextBlock" xlink:title="DebtPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_DebtPolicyTextBlock_lbl">Convertible Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtPolicyTextBlock" xlink:to="us-gaap_DebtPolicyTextBlock_lbl" xlink:title="label: DebtPolicyTextBlock to us-gaap_DebtPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_DebtPolicyTextBlock_lbl1">Debt, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtPolicyTextBlock" xlink:to="us-gaap_DebtPolicyTextBlock_lbl1" xlink:title="label: DebtPolicyTextBlock to us-gaap_DebtPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtSecuritiesMember" xlink:label="DebtSecuritiesMember" xlink:title="DebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtSecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesMember_lbl">Available-for-sale Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesMember" xlink:to="us-gaap_DebtSecuritiesMember_lbl" xlink:title="label: DebtSecuritiesMember to us-gaap_DebtSecuritiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesMember_lbl1">Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesMember" xlink:to="us-gaap_DebtSecuritiesMember_lbl1" xlink:title="label: DebtSecuritiesMember to us-gaap_DebtSecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DeferredFinanceCostsNet" xlink:label="DeferredFinanceCostsNet" xlink:title="DeferredFinanceCostsNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredFinanceCostsNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DeferredFinanceCostsNet_lbl" xml:lang="en-US" id="us-gaap_DeferredFinanceCostsNet_lbl">Unamortized debt issuance costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredFinanceCostsNet" xlink:to="us-gaap_DeferredFinanceCostsNet_lbl" xlink:title="label: DeferredFinanceCostsNet to us-gaap_DeferredFinanceCostsNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredFinanceCostsNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DeferredFinanceCostsNet_lbl1" xml:lang="en-US" id="us-gaap_DeferredFinanceCostsNet_lbl1">Debt Issuance Costs, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredFinanceCostsNet" xlink:to="us-gaap_DeferredFinanceCostsNet_lbl1" xlink:title="label: DeferredFinanceCostsNet to us-gaap_DeferredFinanceCostsNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_Depreciation" xlink:label="Depreciation" xlink:title="Depreciation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Depreciation_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_Depreciation_lbl" xml:lang="en-US" id="us-gaap_Depreciation_lbl">Depreciation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Depreciation" xlink:to="us-gaap_Depreciation_lbl" xlink:title="label: Depreciation to us-gaap_Depreciation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Depreciation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Depreciation_lbl1" xml:lang="en-US" id="us-gaap_Depreciation_lbl1">Depreciation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Depreciation" xlink:to="us-gaap_Depreciation_lbl1" xlink:title="label: Depreciation to us-gaap_Depreciation_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_DerivativesPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DerivativesPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_DerivativesPolicyTextBlock_lbl">Call Spread</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EarningsPerShareBasic" xlink:label="EarningsPerShareBasic" xlink:title="EarningsPerShareBasic" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EarningsPerShareBasicLineItems" xlink:label="EarningsPerShareBasicLineItems" xlink:title="EarningsPerShareBasicLineItems" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EarningsPerShareBasicLineItems" xlink:to="us-gaap_EarningsPerShareBasicLineItems_lbl" xlink:title="label: EarningsPerShareBasicLineItems to us-gaap_EarningsPerShareBasicLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xlink:label="EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xlink:title="EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract_lbl" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="EmployeeStockOptionMember" xlink:title="EmployeeStockOptionMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockOptionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeStockOptionMember_lbl" xml:lang="en-US" id="us-gaap_EmployeeStockOptionMember_lbl">Stock Options [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember_lbl" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockOptionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeStockOptionMember_lbl1" xml:lang="en-US" id="us-gaap_EmployeeStockOptionMember_lbl1">Share-Based Payment Arrangement, Option [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember_lbl1" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:title="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_lbl" xlink:title="label: EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems to us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeStockMember" xlink:label="EmployeeStockMember" xlink:title="EmployeeStockMember" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="EmployeeRelatedLiabilitiesCurrent" xlink:title="EmployeeRelatedLiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl" xml:lang="en-US" id="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl">Accrued compensation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeRelatedLiabilitiesCurrent" xlink:to="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl" xlink:title="label: EmployeeRelatedLiabilitiesCurrent to us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNi_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFvNi_lbl2" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNi_lbl2">Equity Securities, FV-NI, Current</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiCost_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFvNiCost_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiCost_lbl1">Equity Securities, FV-NI, Cost</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1">Equity Securities, FV-NI, Unrealized Loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiUnrealizedLoss" xlink:to="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" xlink:title="label: EquitySecuritiesFvNiUnrealizedLoss to us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EquitySecuritiesFVNIAbstract" xlink:label="EquitySecuritiesFVNIAbstract" xlink:title="EquitySecuritiesFVNIAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFVNIAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesFVNIAbstract_lbl" xml:lang="en-US" id="us-gaap_EquitySecuritiesFVNIAbstract_lbl">Equity Securities [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFVNIAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFVNIAbstract_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFVNIAbstract_lbl1">Equity Securities, FV-NI [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFVNIAbstract" xlink:to="us-gaap_EquitySecuritiesFVNIAbstract_lbl1" xlink:title="label: EquitySecuritiesFVNIAbstract to us-gaap_EquitySecuritiesFVNIAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EquityComponentDomain" xlink:label="EquityComponentDomain" xlink:title="EquityComponentDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquityComponentDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquityComponentDomain_lbl" xml:lang="en-US" id="us-gaap_EquityComponentDomain_lbl">Equity Component [Domain]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EquitySecuritiesMember" xlink:label="EquitySecuritiesMember" xlink:title="EquitySecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_EquitySecuritiesMember_lbl">Equity Securities [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesMember_lbl1">Equity Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesMember" xlink:to="us-gaap_EquitySecuritiesMember_lbl1" xlink:title="label: EquitySecuritiesMember to us-gaap_EquitySecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueNetAssetLiabilityAbstract" xlink:label="FairValueNetAssetLiabilityAbstract" xlink:title="FairValueNetAssetLiabilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueNetAssetLiabilityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueNetAssetLiabilityAbstract_lbl" xml:lang="en-US" id="us-gaap_FairValueNetAssetLiabilityAbstract_lbl">Fair Value Measurements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_FairValueNetAssetLiabilityAbstract_lbl" xlink:title="label: FairValueNetAssetLiabilityAbstract to us-gaap_FairValueNetAssetLiabilityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xml:lang="en-US" id="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1">Fair Value, Net Asset (Liability) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xlink:title="label: FairValueNetAssetLiabilityAbstract to us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueByMeasurementFrequencyAxis" xlink:label="FairValueByMeasurementFrequencyAxis" xlink:title="FairValueByMeasurementFrequencyAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueByMeasurementFrequencyAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueByMeasurementFrequencyAxis_lbl" xml:lang="en-US" id="us-gaap_FairValueByMeasurementFrequencyAxis_lbl">Measurement Frequency [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueByMeasurementFrequencyAxis" xlink:to="us-gaap_FairValueByMeasurementFrequencyAxis_lbl" xlink:title="label: FairValueByMeasurementFrequencyAxis to us-gaap_FairValueByMeasurementFrequencyAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:title="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl" xlink:title="label: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl1" xml:lang="en-US" id="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl1">Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueDisclosuresAbstract" xlink:label="FairValueDisclosuresAbstract" xlink:title="FairValueDisclosuresAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueDisclosuresAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueDisclosuresAbstract_lbl" xml:lang="en-US" id="us-gaap_FairValueDisclosuresAbstract_lbl">Fair Value Measurements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueDisclosuresAbstract" xlink:to="us-gaap_FairValueDisclosuresAbstract_lbl" xlink:title="label: FairValueDisclosuresAbstract to us-gaap_FairValueDisclosuresAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:label="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:title="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_lbl" xml:lang="en-US" id="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_lbl">Fair Value Measurements, Recurring and Nonrecurring [Table]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel1Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueInputsLevel1Member_lbl1" xml:lang="en-US" id="us-gaap_FairValueInputsLevel1Member_lbl1">Fair Value, Inputs, Level 1 [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel2Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueInputsLevel2Member_lbl1" xml:lang="en-US" id="us-gaap_FairValueInputsLevel2Member_lbl1">Fair Value, Inputs, Level 2 [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel3Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueInputsLevel3Member_lbl1" xml:lang="en-US" id="us-gaap_FairValueInputsLevel3Member_lbl1">Fair Value, Inputs, Level 3 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueInputsLevel3Member" xlink:to="us-gaap_FairValueInputsLevel3Member_lbl1" xlink:title="label: FairValueInputsLevel3Member to us-gaap_FairValueInputsLevel3Member_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_FinancialInstrumentAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FinancialInstrumentAxis_lbl" xml:lang="en-US" id="us-gaap_FinancialInstrumentAxis_lbl">Financial Instrument [Axis]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FiniteLivedIntangibleAssetsNet_lbl" xml:lang="en-US" id="us-gaap_FiniteLivedIntangibleAssetsNet_lbl">Patents, net</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1">Increase (Decrease) in Other Operating Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherOperatingAssets" xlink:to="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xlink:title="label: IncreaseDecreaseInOtherOperatingAssets to us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:label="IncreaseDecreaseInOperatingCapitalAbstract" xlink:title="IncreaseDecreaseInOperatingCapitalAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl">Changes in operating assets and liabilities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl" xlink:title="label: IncreaseDecreaseInOperatingCapitalAbstract to us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1">Increase (Decrease) in Operating Capital [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1" xlink:title="label: IncreaseDecreaseInOperatingCapitalAbstract to us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:label="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:title="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl">Accrued compensation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:to="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" xlink:title="label: IncreaseDecreaseInOtherEmployeeRelatedLiabilities to us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1">Increase (Decrease) in Other Employee-Related Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:to="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xlink:title="label: IncreaseDecreaseInOtherEmployeeRelatedLiabilities to us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:label="IncreaseDecreaseInStockholdersEquityRollForward" xlink:title="IncreaseDecreaseInStockholdersEquityRollForward" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl">Increase (Decrease) in Stockholders' Equity [Roll Forward]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl" xlink:title="label: IncreaseDecreaseInStockholdersEquityRollForward to us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1">Increase (Decrease) in Stockholders' Equity [Roll Forward]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xlink:title="label: IncreaseDecreaseInStockholdersEquityRollForward to us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IntangibleAssetsFiniteLivedPolicy" xlink:label="IntangibleAssetsFiniteLivedPolicy" xlink:title="IntangibleAssetsFiniteLivedPolicy" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl" xml:lang="en-US" id="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl">Patent Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IntangibleAssetsFiniteLivedPolicy" xlink:to="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl" xlink:title="label: IntangibleAssetsFiniteLivedPolicy to us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1" xml:lang="en-US" id="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1">Intangible Assets, Finite-Lived, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IntangibleAssetsFiniteLivedPolicy" xlink:to="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1" xlink:title="label: IntangibleAssetsFiniteLivedPolicy to us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestExpense" xlink:label="InterestExpense" xlink:title="InterestExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestExpense_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_InterestExpense_lbl" xml:lang="en-US" id="us-gaap_InterestExpense_lbl">Interest expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpense" xlink:to="us-gaap_InterestExpense_lbl" xlink:title="label: InterestExpense to us-gaap_InterestExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestExpense_lbl1" xml:lang="en-US" id="us-gaap_InterestExpense_lbl1">Interest Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpense" xlink:to="us-gaap_InterestExpense_lbl1" xlink:title="label: InterestExpense to us-gaap_InterestExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestPaidNet" xlink:label="InterestPaidNet" xlink:title="InterestPaidNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPaidNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InterestPaidNet_lbl" xml:lang="en-US" id="us-gaap_InterestPaidNet_lbl">Interest paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPaidNet" xlink:to="us-gaap_InterestPaidNet_lbl" xlink:title="label: InterestPaidNet to us-gaap_InterestPaidNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPaidNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestPaidNet_lbl1" xml:lang="en-US" id="us-gaap_InterestPaidNet_lbl1">Interest Paid, Excluding Capitalized Interest, Operating Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPaidNet" xlink:to="us-gaap_InterestPaidNet_lbl1" xlink:title="label: InterestPaidNet to us-gaap_InterestPaidNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryLineItems" xlink:label="InventoryLineItems" xlink:title="InventoryLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryLineItems_lbl" xml:lang="en-US" id="us-gaap_InventoryLineItems_lbl">Inventory [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryLineItems" xlink:to="us-gaap_InventoryLineItems_lbl" xlink:title="label: InventoryLineItems to us-gaap_InventoryLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryCurrentTable" xlink:label="InventoryCurrentTable" xlink:title="InventoryCurrentTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryCurrentTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryCurrentTable_lbl" xml:lang="en-US" id="us-gaap_InventoryCurrentTable_lbl">Inventory, Current [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryCurrentTable" xlink:to="us-gaap_InventoryCurrentTable_lbl" xlink:title="label: InventoryCurrentTable to us-gaap_InventoryCurrentTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryFinishedGoods" xlink:label="InventoryFinishedGoods" xlink:title="InventoryFinishedGoods" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryFinishedGoods_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryFinishedGoods_lbl" xml:lang="en-US" id="us-gaap_InventoryFinishedGoods_lbl">Finished goods</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryFinishedGoods" xlink:to="us-gaap_InventoryFinishedGoods_lbl" xlink:title="label: InventoryFinishedGoods to us-gaap_InventoryFinishedGoods_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryFinishedGoods_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryFinishedGoods_lbl1" xml:lang="en-US" id="us-gaap_InventoryFinishedGoods_lbl1">Inventory, Finished Goods, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryFinishedGoods" xlink:to="us-gaap_InventoryFinishedGoods_lbl1" xlink:title="label: InventoryFinishedGoods to us-gaap_InventoryFinishedGoods_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryPolicyTextBlock" xlink:label="InventoryPolicyTextBlock" xlink:title="InventoryPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_InventoryPolicyTextBlock_lbl">Inventory Valuation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryPolicyTextBlock" xlink:to="us-gaap_InventoryPolicyTextBlock_lbl" xlink:title="label: InventoryPolicyTextBlock to us-gaap_InventoryPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InventoryPolicyTextBlock_lbl1">Inventory, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryPolicyTextBlock" xlink:to="us-gaap_InventoryPolicyTextBlock_lbl1" xlink:title="label: InventoryPolicyTextBlock to us-gaap_InventoryPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryNet" xlink:label="InventoryNet" xlink:title="InventoryNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryNet_lbl" xml:lang="en-US" id="us-gaap_InventoryNet_lbl">Inventories</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNet" xlink:to="us-gaap_InventoryNet_lbl" xlink:title="label: InventoryNet to us-gaap_InventoryNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_InventoryNet_lbl1" xml:lang="en-US" id="us-gaap_InventoryNet_lbl1">Total inventory</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNet" xlink:to="us-gaap_InventoryNet_lbl1" xlink:title="label: InventoryNet to us-gaap_InventoryNet_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryNet_lbl2" xml:lang="en-US" id="us-gaap_InventoryNet_lbl2">Inventory, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNet" xlink:to="us-gaap_InventoryNet_lbl2" xlink:title="label: InventoryNet to us-gaap_InventoryNet_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryNetAbstract" xlink:label="InventoryNetAbstract" xlink:title="InventoryNetAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNetAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryNetAbstract_lbl" xml:lang="en-US" id="us-gaap_InventoryNetAbstract_lbl">Inventory Valuation [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNetAbstract" xlink:to="us-gaap_InventoryNetAbstract_lbl" xlink:title="label: InventoryNetAbstract to us-gaap_InventoryNetAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNetAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryNetAbstract_lbl1" xml:lang="en-US" id="us-gaap_InventoryNetAbstract_lbl1">Inventory, Net [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNetAbstract" xlink:to="us-gaap_InventoryNetAbstract_lbl1" xlink:title="label: InventoryNetAbstract to us-gaap_InventoryNetAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryRawMaterials" xlink:label="InventoryRawMaterials" xlink:title="InventoryRawMaterials" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryRawMaterials_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryRawMaterials_lbl" xml:lang="en-US" id="us-gaap_InventoryRawMaterials_lbl">Raw materials</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryRawMaterials" xlink:to="us-gaap_InventoryRawMaterials_lbl" xlink:title="label: InventoryRawMaterials to us-gaap_InventoryRawMaterials_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryRawMaterials_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryRawMaterials_lbl1" xml:lang="en-US" id="us-gaap_InventoryRawMaterials_lbl1">Inventory, Raw Materials, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryRawMaterials" xlink:to="us-gaap_InventoryRawMaterials_lbl1" xlink:title="label: InventoryRawMaterials to us-gaap_InventoryRawMaterials_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryWorkInProcess" xlink:label="InventoryWorkInProcess" xlink:title="InventoryWorkInProcess" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWorkInProcess_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryWorkInProcess_lbl" xml:lang="en-US" id="us-gaap_InventoryWorkInProcess_lbl">Work in process</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWorkInProcess" xlink:to="us-gaap_InventoryWorkInProcess_lbl" xlink:title="label: InventoryWorkInProcess to us-gaap_InventoryWorkInProcess_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWorkInProcess_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryWorkInProcess_lbl1" xml:lang="en-US" id="us-gaap_InventoryWorkInProcess_lbl1">Inventory, Work in Process, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWorkInProcess" xlink:to="us-gaap_InventoryWorkInProcess_lbl1" xlink:title="label: InventoryWorkInProcess to us-gaap_InventoryWorkInProcess_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentTextBlock_lbl" xml:lang="en-US" id="us-gaap_InvestmentTextBlock_lbl">Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentTextBlock" xlink:to="us-gaap_InvestmentTextBlock_lbl" xlink:title="label: InvestmentTextBlock to us-gaap_InvestmentTextBlock_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentTextBlock" xlink:to="us-gaap_InvestmentTextBlock_lbl1" xlink:title="label: InvestmentTextBlock to us-gaap_InvestmentTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentHoldingsLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentHoldingsLineItems_lbl" xml:lang="en-US" id="us-gaap_InvestmentHoldingsLineItems_lbl">Investment Holdings [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentHoldingsLineItems" xlink:to="us-gaap_InvestmentHoldingsLineItems_lbl" xlink:title="label: InvestmentHoldingsLineItems to us-gaap_InvestmentHoldingsLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentPolicyTextBlock" xlink:label="InvestmentPolicyTextBlock" xlink:title="InvestmentPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_InvestmentPolicyTextBlock_lbl">Cash, Cash Equivalents and Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentPolicyTextBlock" xlink:to="us-gaap_InvestmentPolicyTextBlock_lbl" xlink:title="label: InvestmentPolicyTextBlock to us-gaap_InvestmentPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InvestmentPolicyTextBlock_lbl1">Investment, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentPolicyTextBlock" xlink:to="us-gaap_InvestmentPolicyTextBlock_lbl1" xlink:title="label: InvestmentPolicyTextBlock to us-gaap_InvestmentPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentIncomeNet" xlink:label="InvestmentIncomeNet" xlink:title="InvestmentIncomeNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentIncomeNet_lbl" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet_lbl">Investment income, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentIncomeNet" xlink:to="us-gaap_InvestmentIncomeNet_lbl" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentHoldingsTable" xlink:label="InvestmentHoldingsTable" xlink:title="InvestmentHoldingsTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentHoldingsTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentHoldingsTable_lbl" xml:lang="en-US" id="us-gaap_InvestmentHoldingsTable_lbl">Investment Holdings [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentHoldingsTable" xlink:to="us-gaap_InvestmentHoldingsTable_lbl" xlink:title="label: InvestmentHoldingsTable to us-gaap_InvestmentHoldingsTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract" xlink:label="InvestmentsDebtAndEquitySecuritiesAbstract" xlink:title="InvestmentsDebtAndEquitySecuritiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl" xml:lang="en-US" id="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl">Available-for-sale and Equity Securities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsDebtAndEquitySecuritiesAbstract" xlink:to="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl" xlink:title="label: InvestmentsDebtAndEquitySecuritiesAbstract to us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl1">Investments, Debt and Equity Securities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsDebtAndEquitySecuritiesAbstract" xlink:to="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl1" xlink:title="label: InvestmentsDebtAndEquitySecuritiesAbstract to us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsAbstract_lbl" xml:lang="en-US" id="us-gaap_InvestmentsAbstract_lbl">Investments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsAbstract" xlink:to="us-gaap_InvestmentsAbstract_lbl" xlink:title="label: InvestmentsAbstract to us-gaap_InvestmentsAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:label="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:title="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl">Contract Maturity of Available-for-Sale Securities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:to="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl" xlink:title="label: InvestmentsClassifiedByContractualMaturityDateTableTextBlock to us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1">Investments Classified by Contractual Maturity Date [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:to="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1" xlink:title="label: InvestmentsClassifiedByContractualMaturityDateTableTextBlock to us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentsAllOtherInvestmentsAbstract" xlink:label="InvestmentsAllOtherInvestmentsAbstract" xlink:title="InvestmentsAllOtherInvestmentsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl" xml:lang="en-US" id="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl">Ownership Interests in Private and Public Companies [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsAllOtherInvestmentsAbstract" xlink:to="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl" xlink:title="label: InvestmentsAllOtherInvestmentsAbstract to us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1" xml:lang="en-US" id="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1">Investments, All Other Investments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsAllOtherInvestmentsAbstract" xlink:to="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1" xlink:title="label: InvestmentsAllOtherInvestmentsAbstract to us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LessorOperatingLeasePaymentsToBeReceived" xlink:label="LessorOperatingLeasePaymentsToBeReceived" xlink:title="LessorOperatingLeasePaymentsToBeReceived" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl" xml:lang="en-US" id="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl">Lease payments to be received over term of sublease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeasePaymentsToBeReceived" xlink:to="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl" xlink:title="label: LessorOperatingLeasePaymentsToBeReceived to us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl1" xml:lang="en-US" id="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl1">Lessor, Operating Lease, Payments to be Received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeasePaymentsToBeReceived" xlink:to="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl1" xlink:title="label: LessorOperatingLeasePaymentsToBeReceived to us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeLeasesPolicyTextBlock" xlink:label="LesseeLeasesPolicyTextBlock" xlink:title="LesseeLeasesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_LesseeLeasesPolicyTextBlock_lbl">Leases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasesPolicyTextBlock" xlink:to="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xlink:title="label: LesseeLeasesPolicyTextBlock to us-gaap_LesseeLeasesPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LesseeLeasesPolicyTextBlock_lbl1">Lessee, Leases [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasesPolicyTextBlock" xlink:to="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xlink:title="label: LesseeLeasesPolicyTextBlock to us-gaap_LesseeLeasesPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm" xlink:label="LesseeOperatingLeaseRenewalTerm" xlink:title="LesseeOperatingLeaseRenewalTerm" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl">Term of operating lease extension</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseRenewalTerm" xlink:to="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" xlink:title="label: LesseeOperatingLeaseRenewalTerm to us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1">Lessee, Operating Lease, Renewal Term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseRenewalTerm" xlink:to="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" xlink:title="label: LesseeOperatingLeaseRenewalTerm to us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseTermOfContract" xlink:label="LesseeOperatingLeaseTermOfContract" xlink:title="LesseeOperatingLeaseTermOfContract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseTermOfContract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseTermOfContract_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseTermOfContract_lbl">Term of operating lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseTermOfContract" xlink:to="us-gaap_LesseeOperatingLeaseTermOfContract_lbl" xlink:title="label: LesseeOperatingLeaseTermOfContract to us-gaap_LesseeOperatingLeaseTermOfContract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseTermOfContract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseTermOfContract_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseTermOfContract_lbl1">Lessee, Operating Lease, Term of Contract</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeLeaseDescriptionTable" xlink:label="LesseeLeaseDescriptionTable" xlink:title="LesseeLeaseDescriptionTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeaseDescriptionTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeaseDescriptionTable_lbl" xml:lang="en-US" id="us-gaap_LesseeLeaseDescriptionTable_lbl">Lessee, Lease, Description [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeaseDescriptionTable" xlink:to="us-gaap_LesseeLeaseDescriptionTable_lbl" xlink:title="label: LesseeLeaseDescriptionTable to us-gaap_LesseeLeaseDescriptionTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeDisclosureAbstract" xlink:label="LesseeDisclosureAbstract" xlink:title="LesseeDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeDisclosureAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeDisclosureAbstract_lbl" xml:lang="en-US" id="us-gaap_LesseeDisclosureAbstract_lbl">Leases [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeDisclosureAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeDisclosureAbstract_lbl1" xml:lang="en-US" id="us-gaap_LesseeDisclosureAbstract_lbl1">Lessee Disclosure [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeDisclosureAbstract" xlink:to="us-gaap_LesseeDisclosureAbstract_lbl1" xlink:title="label: LesseeDisclosureAbstract to us-gaap_LesseeDisclosureAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeLeaseDescriptionLineItems" xlink:label="LesseeLeaseDescriptionLineItems" xlink:title="LesseeLeaseDescriptionLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeaseDescriptionLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeaseDescriptionLineItems_lbl" xml:lang="en-US" id="us-gaap_LesseeLeaseDescriptionLineItems_lbl">Lessee, Lease, Description [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="us-gaap_LesseeLeaseDescriptionLineItems_lbl" xlink:title="label: LesseeLeaseDescriptionLineItems to us-gaap_LesseeLeaseDescriptionLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDue" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1">Lessee, Operating Lease, Liability, to be Paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDue to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LandMember" xlink:label="LandMember" xlink:title="LandMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LandMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LandMember_lbl" xml:lang="en-US" id="us-gaap_LandMember_lbl">Undeveloped Land in Carlsbad, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LandMember" xlink:to="us-gaap_LandMember_lbl" xlink:title="label: LandMember to us-gaap_LandMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LandMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LandMember_lbl1" xml:lang="en-US" id="us-gaap_LandMember_lbl1">Land [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LandMember" xlink:to="us-gaap_LandMember_lbl1" xlink:title="label: LandMember to us-gaap_LandMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LegalMattersAndContingenciesTextBlock" xlink:label="LegalMattersAndContingenciesTextBlock" xlink:title="LegalMattersAndContingenciesTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LegalMattersAndContingenciesTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LegalMattersAndContingenciesTextBlock_lbl" xml:lang="en-US" id="us-gaap_LegalMattersAndContingenciesTextBlock_lbl">Legal Proceedings</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LegalMattersAndContingenciesTextBlock" xlink:to="us-gaap_LegalMattersAndContingenciesTextBlock_lbl" xlink:title="label: LegalMattersAndContingenciesTextBlock to us-gaap_LegalMattersAndContingenciesTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LegalMattersAndContingenciesTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LegalMattersAndContingenciesTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LegalMattersAndContingenciesTextBlock_lbl1">Legal Matters and Contingencies [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LegalMattersAndContingenciesTextBlock" xlink:to="us-gaap_LegalMattersAndContingenciesTextBlock_lbl1" xlink:title="label: LegalMattersAndContingenciesTextBlock to us-gaap_LegalMattersAndContingenciesTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl">LIABILITIES AND STOCKHOLDERS' EQUITY</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" xlink:title="label: LiabilitiesAndStockholdersEquityAbstract to us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1">Liabilities and Equity [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xlink:title="label: LiabilitiesAndStockholdersEquityAbstract to us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="LiabilitiesAndStockholdersEquity" xlink:title="LiabilitiesAndStockholdersEquity" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LiabilitiesAndStockholdersEquity_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquity_lbl">Total liabilities and stockholders' equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_LiabilitiesAndStockholdersEquity_lbl" xlink:title="label: LiabilitiesAndStockholdersEquity to us-gaap_LiabilitiesAndStockholdersEquity_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquity_lbl1">Liabilities and Equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xlink:title="label: LiabilitiesAndStockholdersEquity to us-gaap_LiabilitiesAndStockholdersEquity_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_Liabilities" xlink:label="Liabilities" xlink:title="Liabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_Liabilities_lbl" xml:lang="en-US" id="us-gaap_Liabilities_lbl">Total liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Liabilities" xlink:to="us-gaap_Liabilities_lbl" xlink:title="label: Liabilities to us-gaap_Liabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Liabilities_lbl1" xml:lang="en-US" id="us-gaap_Liabilities_lbl1">Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Liabilities" xlink:to="us-gaap_Liabilities_lbl1" xlink:title="label: Liabilities to us-gaap_Liabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesCurrent" xlink:label="LiabilitiesCurrent" xlink:title="LiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LiabilitiesCurrent_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesCurrent_lbl">Total current liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrent" xlink:to="us-gaap_LiabilitiesCurrent_lbl" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesCurrent_lbl1">Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrent" xlink:to="us-gaap_LiabilitiesCurrent_lbl1" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesCurrentAbstract" xlink:label="LiabilitiesCurrentAbstract" xlink:title="LiabilitiesCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LiabilitiesCurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesCurrentAbstract_lbl">Current liabilities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrentAbstract" xlink:to="us-gaap_LiabilitiesCurrentAbstract_lbl" xlink:title="label: LiabilitiesCurrentAbstract to us-gaap_LiabilitiesCurrentAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesCurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesCurrentAbstract_lbl1">Liabilities, Current [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrentAbstract" xlink:to="us-gaap_LiabilitiesCurrentAbstract_lbl1" xlink:title="label: LiabilitiesCurrentAbstract to us-gaap_LiabilitiesCurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LitigationSettlementAmountAwardedToOtherParty" xlink:label="LitigationSettlementAmountAwardedToOtherParty" xlink:title="LitigationSettlementAmountAwardedToOtherParty" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl" xml:lang="en-US" id="us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl">Settlement agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LitigationSettlementAmountAwardedToOtherParty" xlink:to="us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl" xlink:title="label: LitigationSettlementAmountAwardedToOtherParty to us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl1" xml:lang="en-US" id="us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl1">Litigation Settlement, Amount Awarded to Other Party</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LitigationSettlementAmountAwardedToOtherParty" xlink:to="us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl1" xlink:title="label: LitigationSettlementAmountAwardedToOtherParty to us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LitigationSettlementExpense" xlink:label="LitigationSettlementExpense" xlink:title="LitigationSettlementExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LitigationSettlementExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LitigationSettlementExpense_lbl" xml:lang="en-US" id="us-gaap_LitigationSettlementExpense_lbl">Litigation settlement expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LitigationSettlementExpense" xlink:to="us-gaap_LitigationSettlementExpense_lbl" xlink:title="label: LitigationSettlementExpense to us-gaap_LitigationSettlementExpense_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:label="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:title="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:to="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl" xlink:title="label: LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract to us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1">Long-Term Debt, by Type, Current and Noncurrent [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:to="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1" xlink:title="label: LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract to us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermLoansFromBank" xlink:label="LongTermLoansFromBank" xlink:title="LongTermLoansFromBank" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermLoansFromBank_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermLoansFromBank_lbl" xml:lang="en-US" id="us-gaap_LongTermLoansFromBank_lbl">Long-term mortgage debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermLoansFromBank" xlink:to="us-gaap_LongTermLoansFromBank_lbl" xlink:title="label: LongTermLoansFromBank to us-gaap_LongTermLoansFromBank_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingencyNumberOfPlaintiffs" xlink:label="LossContingencyNumberOfPlaintiffs" xlink:title="LossContingencyNumberOfPlaintiffs" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingencyNumberOfPlaintiffs_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LossContingencyNumberOfPlaintiffs_lbl" xml:lang="en-US" id="us-gaap_LossContingencyNumberOfPlaintiffs_lbl">Number of plaintiffs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LossContingencyNumberOfPlaintiffs" xlink:to="us-gaap_LossContingencyNumberOfPlaintiffs_lbl" xlink:title="label: LossContingencyNumberOfPlaintiffs to us-gaap_LossContingencyNumberOfPlaintiffs_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingencyNumberOfPlaintiffs_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LossContingencyNumberOfPlaintiffs_lbl1" xml:lang="en-US" id="us-gaap_LossContingencyNumberOfPlaintiffs_lbl1">Loss Contingency, Number of Plaintiffs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LossContingencyNumberOfPlaintiffs" xlink:to="us-gaap_LossContingencyNumberOfPlaintiffs_lbl1" xlink:title="label: LossContingencyNumberOfPlaintiffs to us-gaap_LossContingencyNumberOfPlaintiffs_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingenciesLineItems" xlink:label="LossContingenciesLineItems" xlink:title="LossContingenciesLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingenciesLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LossContingenciesLineItems_lbl" xml:lang="en-US" id="us-gaap_LossContingenciesLineItems_lbl">Loss Contingencies [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LossContingenciesLineItems" xlink:to="us-gaap_LossContingenciesLineItems_lbl" xlink:title="label: LossContingenciesLineItems to us-gaap_LossContingenciesLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingenciesTable" xlink:label="LossContingenciesTable" xlink:title="LossContingenciesTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingenciesTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LossContingenciesTable_lbl" xml:lang="en-US" id="us-gaap_LossContingenciesTable_lbl">Loss Contingencies [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LossContingenciesTable" xlink:to="us-gaap_LossContingenciesTable_lbl" xlink:title="label: LossContingenciesTable to us-gaap_LossContingenciesTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingencyClaimsQuantitiesAbstract" xlink:label="LossContingencyClaimsQuantitiesAbstract" xlink:title="LossContingencyClaimsQuantitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl">Legal Procedings [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LossContingencyClaimsQuantitiesAbstract" xlink:to="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl" xlink:title="label: LossContingencyClaimsQuantitiesAbstract to us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl1">Loss Contingency, Quantities [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingencyRelatedReceivableCarryingValueAdditions" xlink:label="LossContingencyRelatedReceivableCarryingValueAdditions" xlink:title="LossContingencyRelatedReceivableCarryingValueAdditions" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingencyRelatedReceivableCarryingValueAdditions_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LossContingencyRelatedReceivableCarryingValueAdditions_lbl" xml:lang="en-US" id="us-gaap_LossContingencyRelatedReceivableCarryingValueAdditions_lbl">Contribution to settlement agreement by insurance carrier</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingencyRelatedReceivableCarryingValueAdditions_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LossContingencyRelatedReceivableCarryingValueAdditions_lbl1" xml:lang="en-US" id="us-gaap_LossContingencyRelatedReceivableCarryingValueAdditions_lbl1">Loss Contingency, Receivable, Additions</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LossContingencyRelatedReceivableCarryingValueAdditions" xlink:to="us-gaap_LossContingencyRelatedReceivableCarryingValueAdditions_lbl1" xlink:title="label: LossContingencyRelatedReceivableCarryingValueAdditions to us-gaap_LossContingencyRelatedReceivableCarryingValueAdditions_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInFinancingActivitiesAbstract" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1">Net Cash Provided by (Used in) Financing Activities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" xlink:title="label: NetCashProvidedByUsedInFinancingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl">Net cash used in operating activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl" xlink:title="label: NetCashProvidedByUsedInOperatingActivities to us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1">Net Cash Provided by (Used in) Operating Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xlink:title="label: NetCashProvidedByUsedInOperatingActivities to us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl">Net cash (used in) provided by investing activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl" xlink:title="label: NetCashProvidedByUsedInInvestingActivities to us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1">Net Cash Provided by (Used in) Investing Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" xlink:title="label: NetCashProvidedByUsedInInvestingActivities to us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl">Net cash (used in) provided by financing activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl" xlink:title="label: NetCashProvidedByUsedInFinancingActivities to us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1">Net Cash Provided by (Used in) Financing Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" xlink:title="label: NetCashProvidedByUsedInFinancingActivities to us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInInvestingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl">Investing activities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" xlink:title="label: NetCashProvidedByUsedInInvestingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1">Net Cash Provided by (Used in) Investing Activities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" xlink:title="label: NetCashProvidedByUsedInInvestingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl">Operating activities:</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1">Net Cash Provided by (Used in) Operating Activities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" xlink:title="label: NetCashProvidedByUsedInOperatingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetIncomeLoss_lbl" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl">Net loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss_lbl" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetIncomeLoss_lbl1" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl1">Net loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss_lbl1" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetIncomeLoss_lbl2" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl2">Net Income (Loss) Attributable to Parent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss_lbl2" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:label="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:title="NewAccountingPronouncementsPolicyPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl">Recently Adopted Accounting Standards</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:to="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl" xlink:title="label: NewAccountingPronouncementsPolicyPolicyTextBlock to us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1">New Accounting Pronouncements, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:to="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1" xlink:title="label: NewAccountingPronouncementsPolicyPolicyTextBlock to us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NonoperatingIncomeExpenseAbstract" xlink:label="NonoperatingIncomeExpenseAbstract" xlink:title="NonoperatingIncomeExpenseAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NonoperatingIncomeExpenseAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NonoperatingIncomeExpenseAbstract_lbl" xml:lang="en-US" id="us-gaap_NonoperatingIncomeExpenseAbstract_lbl">Other income (expense):</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_NonoperatingIncomeExpenseAbstract_lbl" xlink:title="label: NonoperatingIncomeExpenseAbstract to us-gaap_NonoperatingIncomeExpenseAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" xml:lang="en-US" id="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1">Nonoperating Income (Expense) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" xlink:title="label: NonoperatingIncomeExpenseAbstract to us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NotesPayableFairValueDisclosure" xlink:label="NotesPayableFairValueDisclosure" xlink:title="NotesPayableFairValueDisclosure" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NotesPayableFairValueDisclosure_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NotesPayableFairValueDisclosure_lbl" xml:lang="en-US" id="us-gaap_NotesPayableFairValueDisclosure_lbl">Fair value of convertible notes</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_NotesPayableFairValueDisclosure_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NotesPayableFairValueDisclosure_lbl1" xml:lang="en-US" id="us-gaap_NotesPayableFairValueDisclosure_lbl1">Notes Payable, Fair Value Disclosure</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NotesPayableFairValueDisclosure" xlink:to="us-gaap_NotesPayableFairValueDisclosure_lbl1" xlink:title="label: NotesPayableFairValueDisclosure to us-gaap_NotesPayableFairValueDisclosure_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NumberOfOperatingSegments" xlink:label="NumberOfOperatingSegments" xlink:title="NumberOfOperatingSegments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NumberOfOperatingSegments_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NumberOfOperatingSegments_lbl" xml:lang="en-US" id="us-gaap_NumberOfOperatingSegments_lbl">Number of operating segments</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:label="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:title="OperatingLeaseRightOfUseAssetAmortizationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl">Amortization of right-of-use operating lease assets</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingIncomeLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_OperatingIncomeLoss_lbl" xml:lang="en-US" id="us-gaap_OperatingIncomeLoss_lbl">Loss from operations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingIncomeLoss" xlink:to="us-gaap_OperatingIncomeLoss_lbl" xlink:title="label: OperatingIncomeLoss to us-gaap_OperatingIncomeLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingIncomeLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingIncomeLoss_lbl1" xml:lang="en-US" id="us-gaap_OperatingIncomeLoss_lbl1">Operating Income (Loss)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingIncomeLoss" xlink:to="us-gaap_OperatingIncomeLoss_lbl1" xlink:title="label: OperatingIncomeLoss to us-gaap_OperatingIncomeLoss_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:label="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:title="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherDebtSecuritiesMember" xlink:label="OtherDebtSecuritiesMember" xlink:title="OtherDebtSecuritiesMember" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:label="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:title="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1">Payment, Tax Withholding, Share-Based Payment Arrangement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xlink:title="label: PaymentsRelatedToTaxWithholdingForShareBasedCompensation to us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsOfDebtIssuanceCosts" xlink:label="PaymentsOfDebtIssuanceCosts" xlink:title="PaymentsOfDebtIssuanceCosts" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsOfDebtIssuanceCosts_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_PaymentsOfDebtIssuanceCosts_lbl" xml:lang="en-US" id="us-gaap_PaymentsOfDebtIssuanceCosts_lbl">0 percent convertible senior notes issuance costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsOfDebtIssuanceCosts" xlink:to="us-gaap_PaymentsOfDebtIssuanceCosts_lbl" xlink:title="label: PaymentsOfDebtIssuanceCosts to us-gaap_PaymentsOfDebtIssuanceCosts_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsOfDebtIssuanceCosts_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsOfDebtIssuanceCosts_lbl1" xml:lang="en-US" id="us-gaap_PaymentsOfDebtIssuanceCosts_lbl1">Payments of Debt Issuance Costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsOfDebtIssuanceCosts" xlink:to="us-gaap_PaymentsOfDebtIssuanceCosts_lbl1" xlink:title="label: PaymentsOfDebtIssuanceCosts to us-gaap_PaymentsOfDebtIssuanceCosts_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToAcquireIntangibleAssets" xlink:label="PaymentsToAcquireIntangibleAssets" xlink:title="PaymentsToAcquireIntangibleAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireIntangibleAssets_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_PaymentsToAcquireIntangibleAssets_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquireIntangibleAssets_lbl">Acquisition of licenses and other assets, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireIntangibleAssets" xlink:to="us-gaap_PaymentsToAcquireIntangibleAssets_lbl" xlink:title="label: PaymentsToAcquireIntangibleAssets to us-gaap_PaymentsToAcquireIntangibleAssets_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1">Payments to Acquire Intangible Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireIntangibleAssets" xlink:to="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" xlink:title="label: PaymentsToAcquireIntangibleAssets to us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:label="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:title="PaymentsToAcquireAvailableForSaleSecuritiesDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl">Purchases of short-term investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" xlink:title="label: PaymentsToAcquireAvailableForSaleSecuritiesDebt to us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1">Payments to Acquire Debt Securities, Available-for-Sale</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xlink:title="label: PaymentsToAcquireAvailableForSaleSecuritiesDebt to us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="PaymentsToAcquirePropertyPlantAndEquipment" xlink:title="PaymentsToAcquirePropertyPlantAndEquipment" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl">Purchases of property, plant and equipment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquirePropertyPlantAndEquipment" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" xlink:title="label: PaymentsToAcquirePropertyPlantAndEquipment to us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1">Payments to Acquire Property, Plant, and Equipment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquirePropertyPlantAndEquipment" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" xlink:title="label: PaymentsToAcquirePropertyPlantAndEquipment to us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PerformanceSharesMember" xlink:label="PerformanceSharesMember" xlink:title="PerformanceSharesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PerformanceSharesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PerformanceSharesMember_lbl" xml:lang="en-US" id="us-gaap_PerformanceSharesMember_lbl">PRSUs [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PerformanceSharesMember" xlink:to="us-gaap_PerformanceSharesMember_lbl" xlink:title="label: PerformanceSharesMember to us-gaap_PerformanceSharesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PerformanceSharesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PerformanceSharesMember_lbl1" xml:lang="en-US" id="us-gaap_PerformanceSharesMember_lbl1">Performance Shares [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PerformanceSharesMember" xlink:to="us-gaap_PerformanceSharesMember_lbl1" xlink:title="label: PerformanceSharesMember to us-gaap_PerformanceSharesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromConvertibleDebt" xlink:label="ProceedsFromConvertibleDebt" xlink:title="ProceedsFromConvertibleDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromConvertibleDebt_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromConvertibleDebt_lbl" xml:lang="en-US" id="us-gaap_ProceedsFromConvertibleDebt_lbl">Proceeds from the issuance of 0 percent convertible notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromConvertibleDebt" xlink:to="us-gaap_ProceedsFromConvertibleDebt_lbl" xlink:title="label: ProceedsFromConvertibleDebt to us-gaap_ProceedsFromConvertibleDebt_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromConvertibleDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromConvertibleDebt_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromConvertibleDebt_lbl1">Proceeds from Convertible Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromConvertibleDebt" xlink:to="us-gaap_ProceedsFromConvertibleDebt_lbl1" xlink:title="label: ProceedsFromConvertibleDebt to us-gaap_ProceedsFromConvertibleDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromIssuanceOfWarrants" xlink:label="ProceedsFromIssuanceOfWarrants" xlink:title="ProceedsFromIssuanceOfWarrants" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfWarrants_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromIssuanceOfWarrants_lbl" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfWarrants_lbl">Proceeds from issuance of warrants</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOfWarrants" xlink:to="us-gaap_ProceedsFromIssuanceOfWarrants_lbl" xlink:title="label: ProceedsFromIssuanceOfWarrants to us-gaap_ProceedsFromIssuanceOfWarrants_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1">Proceeds from Issuance of Warrants</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOfWarrants" xlink:to="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" xlink:title="label: ProceedsFromIssuanceOfWarrants to us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:label="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl" xml:lang="en-US" id="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl">Proceeds from sale of short-term investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:to="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl" xlink:title="label: ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities to us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1">Proceeds from Sale and Maturity of Debt Securities, Available-for-Sale</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:to="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1" xlink:title="label: ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities to us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment" xlink:label="ProceedsFromSaleOfPropertyPlantAndEquipment" xlink:title="ProceedsFromSaleOfPropertyPlantAndEquipment" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_lbl" xml:lang="en-US" id="us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_lbl">Proceeds from sale of property</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfPropertyPlantAndEquipment" xlink:to="us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_lbl" xlink:title="label: ProceedsFromSaleOfPropertyPlantAndEquipment to us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_lbl1">Proceeds from Sale of Property, Plant, and Equipment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfPropertyPlantAndEquipment" xlink:to="us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_lbl1" xlink:title="label: ProceedsFromSaleOfPropertyPlantAndEquipment to us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:label="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:title="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl">Proceeds from equity, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:to="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl" xlink:title="label: ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions to us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl1">Proceeds, Issuance of Shares, Share-Based Payment Arrangement, Including Option Exercised</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:to="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl1" xlink:title="label: ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions to us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProductMember" xlink:label="ProductMember" xlink:title="ProductMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProductMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProductMember_lbl" xml:lang="en-US" id="us-gaap_ProductMember_lbl">TEGSEDI and WAYLIVRA Revenue, Net [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductMember" xlink:to="us-gaap_ProductMember_lbl" xlink:title="label: ProductMember to us-gaap_ProductMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProductMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProductMember_lbl1" xml:lang="en-US" id="us-gaap_ProductMember_lbl1">Product [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductMember" xlink:to="us-gaap_ProductMember_lbl1" xlink:title="label: ProductMember to us-gaap_ProductMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="PropertyPlantAndEquipmentByTypeAxis" xlink:title="PropertyPlantAndEquipmentByTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl">Long-Lived Tangible Asset [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentByTypeAxis" xlink:to="us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl" xlink:title="label: PropertyPlantAndEquipmentByTypeAxis to us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="PropertyPlantAndEquipmentNet" xlink:title="PropertyPlantAndEquipmentNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentNet_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentNet_lbl">Property, plant and equipment, net</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentNet_lbl1" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentNet_lbl1">Property, Plant and Equipment, Net</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PublicUtilitiesInventoryAxis" xlink:label="PublicUtilitiesInventoryAxis" xlink:title="PublicUtilitiesInventoryAxis" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ResearchAndDevelopmentExpensePolicy" xlink:label="ResearchAndDevelopmentExpensePolicy" xlink:title="ResearchAndDevelopmentExpensePolicy" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueFromContractWithCustomerAbstract" xlink:label="RevenueFromContractWithCustomerAbstract" xlink:title="RevenueFromContractWithCustomerAbstract" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueRecognitionPolicyTextBlock" xlink:label="RevenueRecognitionPolicyTextBlock" xlink:title="RevenueRecognitionPolicyTextBlock" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenuesAbstract" xlink:label="RevenuesAbstract" xlink:title="RevenuesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenuesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenuesAbstract_lbl" xml:lang="en-US" id="us-gaap_RevenuesAbstract_lbl">Revenue:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenuesAbstract" xlink:to="us-gaap_RevenuesAbstract_lbl" xlink:title="label: RevenuesAbstract to us-gaap_RevenuesAbstract_lbl" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl1" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl">Vesting percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Award Vesting Rights, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl">Expected life</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1 to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Fair Value Assumptions, Expected Term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1 to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:label="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:title="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl">Weighted-Average Assumptions for ESPP</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:to="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl" xlink:title="label: ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock to us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl1">Schedule of Share-Based Payment Award, Employee Stock Purchase Plan, Valuation Assumptions [Table Text Block]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" xlink:label="ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" xlink:title="ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl">Temporarily Impaired Investments</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl1">Schedule of Temporary Impairment Losses, Investments [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" xlink:to="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl1" xlink:title="label: ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock to us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:label="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:title="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:to="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl" xlink:title="label: ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock to us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl1">Schedule of Share-Based Payment Award, Stock Options, Valuation Assumptions [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:to="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl1" xlink:title="label: ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock to us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:title="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfInventoryCurrentTableTextBlock" xlink:label="ScheduleOfInventoryCurrentTableTextBlock" xlink:title="ScheduleOfInventoryCurrentTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl">Inventory</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:to="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable_lbl" xlink:title="label: ScheduleOfEarningsPerShareBasicByCommonClassTable to us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable_lbl" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:label="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:title="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:to="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_lbl" xlink:title="label: ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable to us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:title="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" xlink:to="us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl1" xlink:title="label: SchedulesOfConcentrationOfRiskByRiskFactorTextBlock to us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:label="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:title="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:label="SellingGeneralAndAdministrativeExpensesMember" xlink:title="SellingGeneralAndAdministrativeExpensesMember" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1">Selling, General and Administrative Expenses [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpense_lbl1" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpense_lbl1">Selling, General and Administrative Expense</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_SharesIssued_lbl" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_SharesIssued_lbl" xml:lang="en-US" id="us-gaap_SharesIssued_lbl">Balance (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued_lbl" xlink:title="label: SharesIssued to us-gaap_SharesIssued_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesIssued_lbl1" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_SharesIssued_lbl1" xml:lang="en-US" id="us-gaap_SharesIssued_lbl1">Balance (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued_lbl1" xlink:title="label: SharesIssued to us-gaap_SharesIssued_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesIssued_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharesIssued_lbl2" xml:lang="en-US" id="us-gaap_SharesIssued_lbl2">Shares, Issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued_lbl2" xlink:title="label: SharesIssued to us-gaap_SharesIssued_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShortTermInvestments" xlink:label="ShortTermInvestments" xlink:title="ShortTermInvestments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShortTermInvestments_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShortTermInvestments_lbl" xml:lang="en-US" id="us-gaap_ShortTermInvestments_lbl">Short-term investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShortTermInvestments" xlink:to="us-gaap_ShortTermInvestments_lbl" xlink:title="label: ShortTermInvestments to us-gaap_ShortTermInvestments_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShortTermInvestments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShortTermInvestments_lbl1" xml:lang="en-US" id="us-gaap_ShortTermInvestments_lbl1">Short-Term Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShortTermInvestments" xlink:to="us-gaap_ShortTermInvestments_lbl1" xlink:title="label: ShortTermInvestments to us-gaap_ShortTermInvestments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SignificantAccountingPoliciesTextBlock" xlink:label="SignificantAccountingPoliciesTextBlock" xlink:title="SignificantAccountingPoliciesTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SignificantAccountingPoliciesTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SignificantAccountingPoliciesTextBlock_lbl" xml:lang="en-US" id="us-gaap_SignificantAccountingPoliciesTextBlock_lbl">Significant Accounting Policies</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantAccountingPoliciesTextBlock" xlink:to="us-gaap_SignificantAccountingPoliciesTextBlock_lbl" xlink:title="label: SignificantAccountingPoliciesTextBlock to us-gaap_SignificantAccountingPoliciesTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SignificantAccountingPoliciesTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SignificantAccountingPoliciesTextBlock_lbl1" xml:lang="en-US" id="us-gaap_SignificantAccountingPoliciesTextBlock_lbl1">Significant Accounting Policies [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantAccountingPoliciesTextBlock" xlink:to="us-gaap_SignificantAccountingPoliciesTextBlock_lbl1" xlink:title="label: SignificantAccountingPoliciesTextBlock to us-gaap_SignificantAccountingPoliciesTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementOfFinancialPositionAbstract" xlink:label="StatementOfFinancialPositionAbstract" xlink:title="StatementOfFinancialPositionAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfFinancialPositionAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfFinancialPositionAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfFinancialPositionAbstract_lbl">CONSOLIDATED BALANCE SHEETS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfFinancialPositionAbstract" xlink:to="us-gaap_StatementOfFinancialPositionAbstract_lbl" xlink:title="label: StatementOfFinancialPositionAbstract to us-gaap_StatementOfFinancialPositionAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:label="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:title="StatementOfIncomeAndComprehensiveIncomeAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl">CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xlink:title="label: StatementOfIncomeAndComprehensiveIncomeAbstract to us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="StatementEquityComponentsAxis" xlink:title="StatementEquityComponentsAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementEquityComponentsAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementEquityComponentsAxis_lbl" xml:lang="en-US" id="us-gaap_StatementEquityComponentsAxis_lbl">Equity Components [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementEquityComponentsAxis" xlink:to="us-gaap_StatementEquityComponentsAxis_lbl" xlink:title="label: StatementEquityComponentsAxis to us-gaap_StatementEquityComponentsAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementLineItems_lbl" xml:lang="en-US" id="us-gaap_StatementLineItems_lbl">Statement [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementLineItems" xlink:to="us-gaap_StatementLineItems_lbl" xlink:title="label: StatementLineItems to us-gaap_StatementLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementOfCashFlowsAbstract" xlink:label="StatementOfCashFlowsAbstract" xlink:title="StatementOfCashFlowsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfCashFlowsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfCashFlowsAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfCashFlowsAbstract_lbl">CONSOLIDATED STATEMENTS OF CASH FLOWS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfCashFlowsAbstract" xlink:to="us-gaap_StatementOfCashFlowsAbstract_lbl" xlink:title="label: StatementOfCashFlowsAbstract to us-gaap_StatementOfCashFlowsAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementTable_lbl" xml:lang="en-US" id="us-gaap_StatementTable_lbl">Statement [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementTable" xlink:to="us-gaap_StatementTable_lbl" xlink:title="label: StatementTable to us-gaap_StatementTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementOfStockholdersEquityAbstract" xlink:label="StatementOfStockholdersEquityAbstract" xlink:title="StatementOfStockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfStockholdersEquityAbstract_lbl">CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfStockholdersEquityAbstract" xlink:to="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xlink:title="label: StatementOfStockholdersEquityAbstract to us-gaap_StatementOfStockholdersEquityAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:label="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:title="StockIssuedDuringPeriodValueShareBasedCompensationGross" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl">Issuance of common stock in connection with employee stock plans</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xlink:title="label: StockIssuedDuringPeriodValueShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1">Shares Issued, Value, Share-Based Payment Arrangement, before Forfeiture</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xlink:title="label: StockIssuedDuringPeriodValueShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:label="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:title="StockIssuedDuringPeriodSharesShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl">Issuance of common stock in connection with employee stock plans (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensation to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1">Shares Issued, Shares, Share-Based Payment Arrangement, after Forfeiture</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensation to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockholdersEquity" xlink:label="StockholdersEquity" xlink:title="StockholdersEquity" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquity_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_StockholdersEquity_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquity_lbl">Total stockholders' equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquity" xlink:to="us-gaap_StockholdersEquity_lbl" xlink:title="label: StockholdersEquity to us-gaap_StockholdersEquity_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquity_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockholdersEquity_lbl1" xml:lang="en-US" id="us-gaap_StockholdersEquity_lbl1">Stockholders' Equity Attributable to Parent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquity" xlink:to="us-gaap_StockholdersEquity_lbl1" xlink:title="label: StockholdersEquity to us-gaap_StockholdersEquity_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:label="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:title="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl">Balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1">Balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2">Stockholders' Equity, Including Portion Attributable to Noncontrolling Interest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockholdersEquityAbstract" xlink:label="StockholdersEquityAbstract" xlink:title="StockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockholdersEquityAbstract_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquityAbstract_lbl">Stockholders' equity:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityAbstract" xlink:to="us-gaap_StockholdersEquityAbstract_lbl" xlink:title="label: StockholdersEquityAbstract to us-gaap_StockholdersEquityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockholdersEquityAbstract_lbl1" xml:lang="en-US" id="us-gaap_StockholdersEquityAbstract_lbl1">Stockholders' Equity Attributable to Parent [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityAbstract" xlink:to="us-gaap_StockholdersEquityAbstract_lbl1" xlink:title="label: StockholdersEquityAbstract to us-gaap_StockholdersEquityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="SubsequentEventTypeDomain" xlink:title="SubsequentEventTypeDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventTypeDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventTypeDomain_lbl" xml:lang="en-US" id="us-gaap_SubsequentEventTypeDomain_lbl">Subsequent Event Type [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SubsequentEventTypeDomain" xlink:to="us-gaap_SubsequentEventTypeDomain_lbl" xlink:title="label: SubsequentEventTypeDomain to us-gaap_SubsequentEventTypeDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SubsequentEventMember" xlink:label="SubsequentEventMember" xlink:title="SubsequentEventMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventMember_lbl" xml:lang="en-US" id="us-gaap_SubsequentEventMember_lbl">Subsequent Event [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SubsequentEventMember" xlink:to="us-gaap_SubsequentEventMember_lbl" xlink:title="label: SubsequentEventMember to us-gaap_SubsequentEventMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="SubsequentEventTypeAxis" xlink:title="SubsequentEventTypeAxis" />
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    <link:label xlink:type="resource" xlink:label="srt_NameOfMajorCustomerDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_NameOfMajorCustomerDomain_lbl" xml:lang="en-US" id="srt_NameOfMajorCustomerDomain_lbl">Customer [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NameOfMajorCustomerDomain" xlink:to="srt_NameOfMajorCustomerDomain_lbl" xlink:title="label: NameOfMajorCustomerDomain to srt_NameOfMajorCustomerDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ProductsAndServicesDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductsAndServicesDomain_lbl" xml:lang="en-US" id="srt_ProductsAndServicesDomain_lbl">Products and Services [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductsAndServicesDomain" xlink:to="srt_ProductsAndServicesDomain_lbl" xlink:title="label: ProductsAndServicesDomain to srt_ProductsAndServicesDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:label xlink:type="resource" xlink:label="srt_ProductOrServiceAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductOrServiceAxis_lbl" xml:lang="en-US" id="srt_ProductOrServiceAxis_lbl">Products and Services [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductOrServiceAxis" xlink:to="srt_ProductOrServiceAxis_lbl" xlink:title="label: ProductOrServiceAxis to srt_ProductOrServiceAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:label xlink:type="resource" xlink:label="srt_RangeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RangeAxis_lbl" xml:lang="en-US" id="srt_RangeAxis_lbl">Statistical Measurement [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RangeAxis" xlink:to="srt_RangeAxis_lbl" xlink:title="label: RangeAxis to srt_RangeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:label xlink:type="resource" xlink:label="srt_RangeMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RangeMember_lbl" xml:lang="en-US" id="srt_RangeMember_lbl">Statistical Measurement [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RangeMember" xlink:to="srt_RangeMember_lbl" xlink:title="label: RangeMember to srt_RangeMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ScenarioForecastMember" xlink:label="ScenarioForecastMember" xlink:title="ScenarioForecastMember" />
    <link:label xlink:type="resource" xlink:label="srt_ScenarioForecastMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ScenarioForecastMember_lbl" xml:lang="en-US" id="srt_ScenarioForecastMember_lbl">Forecast [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScenarioForecastMember" xlink:to="srt_ScenarioForecastMember_lbl" xlink:title="label: ScenarioForecastMember to srt_ScenarioForecastMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain" xlink:title="ScenarioUnspecifiedDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ScenarioUnspecifiedDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ScenarioUnspecifiedDomain_lbl" xml:lang="en-US" id="srt_ScenarioUnspecifiedDomain_lbl">Scenario [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScenarioUnspecifiedDomain" xlink:to="srt_ScenarioUnspecifiedDomain_lbl" xlink:title="label: ScenarioUnspecifiedDomain to srt_ScenarioUnspecifiedDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_StatementScenarioAxis" xlink:label="StatementScenarioAxis" xlink:title="StatementScenarioAxis" />
    <link:label xlink:type="resource" xlink:label="srt_StatementScenarioAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_StatementScenarioAxis_lbl" xml:lang="en-US" id="srt_StatementScenarioAxis_lbl">Scenario [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementScenarioAxis" xlink:to="srt_StatementScenarioAxis_lbl" xlink:title="label: StatementScenarioAxis to srt_StatementScenarioAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_CoverAbstract" xlink:label="CoverAbstract" xlink:title="CoverAbstract" />
    <link:label xlink:type="resource" xlink:label="dei_CoverAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CoverAbstract_lbl" xml:lang="en-US" id="dei_CoverAbstract_lbl">Cover [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CoverAbstract" xlink:to="dei_CoverAbstract_lbl" xlink:title="label: CoverAbstract to dei_CoverAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentType" xlink:label="DocumentType" xlink:title="DocumentType" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentType_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentType_lbl" xml:lang="en-US" id="dei_DocumentType_lbl">Document Type</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentType" xlink:to="dei_DocumentType_lbl" xlink:title="label: DocumentType to dei_DocumentType_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentQuarterlyReport" xlink:label="DocumentQuarterlyReport" xlink:title="DocumentQuarterlyReport" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentQuarterlyReport_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentQuarterlyReport_lbl" xml:lang="en-US" id="dei_DocumentQuarterlyReport_lbl">Document Quarterly Report</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentQuarterlyReport" xlink:to="dei_DocumentQuarterlyReport_lbl" xlink:title="label: DocumentQuarterlyReport to dei_DocumentQuarterlyReport_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentTransitionReport" xlink:label="DocumentTransitionReport" xlink:title="DocumentTransitionReport" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentTransitionReport_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentTransitionReport_lbl" xml:lang="en-US" id="dei_DocumentTransitionReport_lbl">Document Transition Report</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentTransitionReport" xlink:to="dei_DocumentTransitionReport_lbl" xlink:title="label: DocumentTransitionReport to dei_DocumentTransitionReport_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityInteractiveDataCurrent" xlink:label="EntityInteractiveDataCurrent" xlink:title="EntityInteractiveDataCurrent" />
    <link:label xlink:type="resource" xlink:label="dei_EntityInteractiveDataCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityInteractiveDataCurrent_lbl" xml:lang="en-US" id="dei_EntityInteractiveDataCurrent_lbl">Entity Interactive Data Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityInteractiveDataCurrent" xlink:to="dei_EntityInteractiveDataCurrent_lbl" xlink:title="label: EntityInteractiveDataCurrent to dei_EntityInteractiveDataCurrent_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_AmendmentFlag" xlink:label="AmendmentFlag" xlink:title="AmendmentFlag" />
    <link:label xlink:type="resource" xlink:label="dei_AmendmentFlag_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AmendmentFlag_lbl" xml:lang="en-US" id="dei_AmendmentFlag_lbl">Amendment Flag</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmendmentFlag" xlink:to="dei_AmendmentFlag_lbl" xlink:title="label: AmendmentFlag to dei_AmendmentFlag_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentFiscalYearFocus" xlink:label="DocumentFiscalYearFocus" xlink:title="DocumentFiscalYearFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalYearFocus_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalYearFocus_lbl" xml:lang="en-US" id="dei_DocumentFiscalYearFocus_lbl">Document Fiscal Year Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalYearFocus" xlink:to="dei_DocumentFiscalYearFocus_lbl" xlink:title="label: DocumentFiscalYearFocus to dei_DocumentFiscalYearFocus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentFiscalPeriodFocus" xlink:label="DocumentFiscalPeriodFocus" xlink:title="DocumentFiscalPeriodFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalPeriodFocus_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalPeriodFocus_lbl" xml:lang="en-US" id="dei_DocumentFiscalPeriodFocus_lbl">Document Fiscal Period Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalPeriodFocus" xlink:to="dei_DocumentFiscalPeriodFocus_lbl" xlink:title="label: DocumentFiscalPeriodFocus to dei_DocumentFiscalPeriodFocus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentPeriodEndDate" xlink:label="DocumentPeriodEndDate" xlink:title="DocumentPeriodEndDate" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentPeriodEndDate_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentPeriodEndDate_lbl" xml:lang="en-US" id="dei_DocumentPeriodEndDate_lbl">Document Period End Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentPeriodEndDate" xlink:to="dei_DocumentPeriodEndDate_lbl" xlink:title="label: DocumentPeriodEndDate to dei_DocumentPeriodEndDate_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityRegistrantName" xlink:label="EntityRegistrantName" xlink:title="EntityRegistrantName" />
    <link:label xlink:type="resource" xlink:label="dei_EntityRegistrantName_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityRegistrantName_lbl" xml:lang="en-US" id="dei_EntityRegistrantName_lbl">Entity Registrant Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityRegistrantName" xlink:to="dei_EntityRegistrantName_lbl" xlink:title="label: EntityRegistrantName to dei_EntityRegistrantName_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityCentralIndexKey" xlink:label="EntityCentralIndexKey" xlink:title="EntityCentralIndexKey" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCentralIndexKey_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCentralIndexKey_lbl" xml:lang="en-US" id="dei_EntityCentralIndexKey_lbl">Entity Central Index Key</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCentralIndexKey" xlink:to="dei_EntityCentralIndexKey_lbl" xlink:title="label: EntityCentralIndexKey to dei_EntityCentralIndexKey_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityFileNumber" xlink:label="EntityFileNumber" xlink:title="EntityFileNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFileNumber_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFileNumber_lbl" xml:lang="en-US" id="dei_EntityFileNumber_lbl">Entity File Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityFileNumber" xlink:to="dei_EntityFileNumber_lbl" xlink:title="label: EntityFileNumber to dei_EntityFileNumber_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityTaxIdentificationNumber" xlink:label="EntityTaxIdentificationNumber" xlink:title="EntityTaxIdentificationNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityTaxIdentificationNumber_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityTaxIdentificationNumber_lbl" xml:lang="en-US" id="dei_EntityTaxIdentificationNumber_lbl">Entity Tax Identification Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityTaxIdentificationNumber" xlink:to="dei_EntityTaxIdentificationNumber_lbl" xlink:title="label: EntityTaxIdentificationNumber to dei_EntityTaxIdentificationNumber_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityIncorporationStateCountryCode" xlink:label="EntityIncorporationStateCountryCode" xlink:title="EntityIncorporationStateCountryCode" />
    <link:label xlink:type="resource" xlink:label="dei_EntityIncorporationStateCountryCode_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityIncorporationStateCountryCode_lbl" xml:lang="en-US" id="dei_EntityIncorporationStateCountryCode_lbl">Entity Incorporation, State or Country Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityIncorporationStateCountryCode" xlink:to="dei_EntityIncorporationStateCountryCode_lbl" xlink:title="label: EntityIncorporationStateCountryCode to dei_EntityIncorporationStateCountryCode_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_CurrentFiscalYearEndDate" xlink:label="CurrentFiscalYearEndDate" xlink:title="CurrentFiscalYearEndDate" />
    <link:label xlink:type="resource" xlink:label="dei_CurrentFiscalYearEndDate_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CurrentFiscalYearEndDate_lbl" xml:lang="en-US" id="dei_CurrentFiscalYearEndDate_lbl">Current Fiscal Year End Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentFiscalYearEndDate" xlink:to="dei_CurrentFiscalYearEndDate_lbl" xlink:title="label: CurrentFiscalYearEndDate to dei_CurrentFiscalYearEndDate_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityCurrentReportingStatus" xlink:label="EntityCurrentReportingStatus" xlink:title="EntityCurrentReportingStatus" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCurrentReportingStatus_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCurrentReportingStatus_lbl" xml:lang="en-US" id="dei_EntityCurrentReportingStatus_lbl">Entity Current Reporting Status</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCurrentReportingStatus" xlink:to="dei_EntityCurrentReportingStatus_lbl" xlink:title="label: EntityCurrentReportingStatus to dei_EntityCurrentReportingStatus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityShellCompany" xlink:label="EntityShellCompany" xlink:title="EntityShellCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityShellCompany_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityShellCompany_lbl" xml:lang="en-US" id="dei_EntityShellCompany_lbl">Entity Shell Company</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityShellCompany" xlink:to="dei_EntityShellCompany_lbl" xlink:title="label: EntityShellCompany to dei_EntityShellCompany_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityFilerCategory" xlink:label="EntityFilerCategory" xlink:title="EntityFilerCategory" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFilerCategory_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFilerCategory_lbl" xml:lang="en-US" id="dei_EntityFilerCategory_lbl">Entity Filer Category</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityFilerCategory" xlink:to="dei_EntityFilerCategory_lbl" xlink:title="label: EntityFilerCategory to dei_EntityFilerCategory_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntitySmallBusiness" xlink:label="EntitySmallBusiness" xlink:title="EntitySmallBusiness" />
    <link:label xlink:type="resource" xlink:label="dei_EntitySmallBusiness_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntitySmallBusiness_lbl" xml:lang="en-US" id="dei_EntitySmallBusiness_lbl">Entity Small Business</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntitySmallBusiness" xlink:to="dei_EntitySmallBusiness_lbl" xlink:title="label: EntitySmallBusiness to dei_EntitySmallBusiness_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityEmergingGrowthCompany" xlink:label="EntityEmergingGrowthCompany" xlink:title="EntityEmergingGrowthCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityEmergingGrowthCompany_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityEmergingGrowthCompany_lbl" xml:lang="en-US" id="dei_EntityEmergingGrowthCompany_lbl">Entity Emerging Growth Company</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityEmergingGrowthCompany" xlink:to="dei_EntityEmergingGrowthCompany_lbl" xlink:title="label: EntityEmergingGrowthCompany to dei_EntityEmergingGrowthCompany_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressAddressLine1" xlink:label="EntityAddressAddressLine1" xlink:title="EntityAddressAddressLine1" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressAddressLine1_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressAddressLine1_lbl" xml:lang="en-US" id="dei_EntityAddressAddressLine1_lbl">Entity Address, Address Line One</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressAddressLine1" xlink:to="dei_EntityAddressAddressLine1_lbl" xlink:title="label: EntityAddressAddressLine1 to dei_EntityAddressAddressLine1_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressCityOrTown" xlink:label="EntityAddressCityOrTown" xlink:title="EntityAddressCityOrTown" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressCityOrTown_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressCityOrTown_lbl" xml:lang="en-US" id="dei_EntityAddressCityOrTown_lbl">Entity Address, City or Town</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressStateOrProvince" xlink:label="EntityAddressStateOrProvince" xlink:title="EntityAddressStateOrProvince" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressStateOrProvince_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressStateOrProvince_lbl" xml:lang="en-US" id="dei_EntityAddressStateOrProvince_lbl">Entity Address, State or Province</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressPostalZipCode" xlink:label="EntityAddressPostalZipCode" xlink:title="EntityAddressPostalZipCode" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressPostalZipCode_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressPostalZipCode_lbl" xml:lang="en-US" id="dei_EntityAddressPostalZipCode_lbl">Entity Address, Postal Zip Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressPostalZipCode" xlink:to="dei_EntityAddressPostalZipCode_lbl" xlink:title="label: EntityAddressPostalZipCode to dei_EntityAddressPostalZipCode_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_CityAreaCode" xlink:label="CityAreaCode" xlink:title="CityAreaCode" />
    <link:label xlink:type="resource" xlink:label="dei_CityAreaCode_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CityAreaCode_lbl" xml:lang="en-US" id="dei_CityAreaCode_lbl">City Area Code</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_LocalPhoneNumber" xlink:label="LocalPhoneNumber" xlink:title="LocalPhoneNumber" />
    <link:label xlink:type="resource" xlink:label="dei_LocalPhoneNumber_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_LocalPhoneNumber_lbl" xml:lang="en-US" id="dei_LocalPhoneNumber_lbl">Local Phone Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LocalPhoneNumber" xlink:to="dei_LocalPhoneNumber_lbl" xlink:title="label: LocalPhoneNumber to dei_LocalPhoneNumber_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_Security12bTitle" xlink:label="Security12bTitle" xlink:title="Security12bTitle" />
    <link:label xlink:type="resource" xlink:label="dei_Security12bTitle_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_Security12bTitle_lbl" xml:lang="en-US" id="dei_Security12bTitle_lbl">Title of 12(b) Security</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Security12bTitle" xlink:to="dei_Security12bTitle_lbl" xlink:title="label: Security12bTitle to dei_Security12bTitle_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_TradingSymbol" xlink:label="TradingSymbol" xlink:title="TradingSymbol" />
    <link:label xlink:type="resource" xlink:label="dei_TradingSymbol_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_TradingSymbol_lbl" xml:lang="en-US" id="dei_TradingSymbol_lbl">Trading Symbol</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TradingSymbol" xlink:to="dei_TradingSymbol_lbl" xlink:title="label: TradingSymbol to dei_TradingSymbol_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_SecurityExchangeName" xlink:label="SecurityExchangeName" xlink:title="SecurityExchangeName" />
    <link:label xlink:type="resource" xlink:label="dei_SecurityExchangeName_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_SecurityExchangeName_lbl" xml:lang="en-US" id="dei_SecurityExchangeName_lbl">Security Exchange Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SecurityExchangeName" xlink:to="dei_SecurityExchangeName_lbl" xlink:title="label: SecurityExchangeName to dei_SecurityExchangeName_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityCommonStockSharesOutstanding" xlink:label="EntityCommonStockSharesOutstanding" xlink:title="EntityCommonStockSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCommonStockSharesOutstanding_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCommonStockSharesOutstanding_lbl" xml:lang="en-US" id="dei_EntityCommonStockSharesOutstanding_lbl">Entity Common Stock, Shares Outstanding</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCommonStockSharesOutstanding" xlink:to="dei_EntityCommonStockSharesOutstanding_lbl" xlink:title="label: EntityCommonStockSharesOutstanding to dei_EntityCommonStockSharesOutstanding_lbl" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:label="LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:title="LongTermObligationsExcludingConvertibleDebtNoncurrent" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl" xml:lang="en-US" id="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl">Amount of long-term debt and lease obligations, excluding convertible debt, classified as noncurrent.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl1" xml:lang="en-US" id="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl1">Long-term Obligations Excluding Convertible Debt, Noncurrent</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl2" xml:lang="en-US" id="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl2">Long-term obligations, less current portion</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:to="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl2" xlink:title="label: LongTermObligationsExcludingConvertibleDebtNoncurrent to ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_LongTermObligationsExcludingConvertibleDebtCurrent" xlink:label="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:title="LongTermObligationsExcludingConvertibleDebtCurrent" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl" xml:lang="en-US" id="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl">Amount of long-term debt and lease obligations, excluding convertible debt, classified as current.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:to="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl" xlink:title="label: LongTermObligationsExcludingConvertibleDebtCurrent to ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl1" xml:lang="en-US" id="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl1">Long-term Obligations, Excluding Convertible Debt, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:to="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl1" xlink:title="label: LongTermObligationsExcludingConvertibleDebtCurrent to ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl2" xml:lang="en-US" id="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl2">Current portion of long-term obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:to="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl2" xlink:title="label: LongTermObligationsExcludingConvertibleDebtCurrent to ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl">0.125 percent convertible senior notes due December 2024.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl1">Convertible Senior Notes 0.125 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl2">0.125% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl3">0.125 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl">0 percent convertible senior notes due April 2026.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl1">Convertible Senior Notes 0 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl2">0 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl3">0% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" xml:lang="en-US" id="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl">Number of privately-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for under the cost method.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:to="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" xlink:title="label: NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment to ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1" xml:lang="en-US" id="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1">Number of Privately-Held Companies in which Entity has Equity Investment</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" xml:lang="en-US" id="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2">Number of privately held companies in which there is an equity ownership interest of less than 20%</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:to="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" xlink:title="label: NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment to ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3" xml:lang="en-US" id="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3">Number of private companies in which there is an equity ownership interest of less than 20%</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:to="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3" xlink:title="label: NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment to ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" xml:lang="en-US" id="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl">Number of publicly-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for at fair value.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl">The percentage of available-for-sale debt securities that mature within one year of the balance sheet date.</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature within two years of the balance sheet date.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, within Two Years, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2">Percentage of available-for-sale securities with a maturity of less than two years</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl">The aggregate percentage of all available-for-sale debt securities, regardless of maturity.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1">Available-for-sale Securities, Debt Maturities, Total, Percentage</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature beyond one year but within two years of the balance sheet date.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, after One Through Two Years, Percentage</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2">After one year but within two years</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature beyond two years but within three and one-half years of the balance sheet date.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, after Two Through Three and One Half Years, Percentage</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_MaximumContractMaturityPeriodRange1" xlink:label="MaximumContractMaturityPeriodRange1" xlink:title="MaximumContractMaturityPeriodRange1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange1_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1_lbl">The maximum contract maturity period for the first range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl">The maximum contract maturity period for the second range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_MaximumContractMaturityPeriodRange3" xlink:label="MaximumContractMaturityPeriodRange3" xlink:title="MaximumContractMaturityPeriodRange3" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange3_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange3_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3_lbl">The maximum contract maturity period for the third range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange3" xlink:to="ions_MaximumContractMaturityPeriodRange3_lbl" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange3" xlink:to="ions_MaximumContractMaturityPeriodRange3_lbl2" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_ResearchDevelopmentAndPatentExpensesMember" xlink:label="ResearchDevelopmentAndPatentExpensesMember" xlink:title="ResearchDevelopmentAndPatentExpensesMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpensesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchDevelopmentAndPatentExpensesMember_lbl" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpensesMember_lbl">Primary financial statement caption encompassing research, development and patent expenses.</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl2" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl2" />
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    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_EplontersenJointDevelopmentRevenueMember" xlink:label="EplontersenJointDevelopmentRevenueMember" xlink:title="EplontersenJointDevelopmentRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_EplontersenJointDevelopmentRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EplontersenJointDevelopmentRevenueMember_lbl" xml:lang="en-US" id="ions_EplontersenJointDevelopmentRevenueMember_lbl">Joint development revenue for eplontersen.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EplontersenJointDevelopmentRevenueMember" xlink:to="ions_EplontersenJointDevelopmentRevenueMember_lbl" xlink:title="label: EplontersenJointDevelopmentRevenueMember to ions_EplontersenJointDevelopmentRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EplontersenJointDevelopmentRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EplontersenJointDevelopmentRevenueMember_lbl1" xml:lang="en-US" id="ions_EplontersenJointDevelopmentRevenueMember_lbl1">Eplontersen Joint Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EplontersenJointDevelopmentRevenueMember" xlink:to="ions_EplontersenJointDevelopmentRevenueMember_lbl1" xlink:title="label: EplontersenJointDevelopmentRevenueMember to ions_EplontersenJointDevelopmentRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EplontersenJointDevelopmentRevenueMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EplontersenJointDevelopmentRevenueMember_lbl2" xml:lang="en-US" id="ions_EplontersenJointDevelopmentRevenueMember_lbl2">Eplontersen Joint Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EplontersenJointDevelopmentRevenueMember" xlink:to="ions_EplontersenJointDevelopmentRevenueMember_lbl2" xlink:title="label: EplontersenJointDevelopmentRevenueMember to ions_EplontersenJointDevelopmentRevenueMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_CommercialMember" xlink:label="CommercialMember" xlink:title="CommercialMember" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CommercialMember_lbl1" xml:lang="en-US" id="ions_CommercialMember_lbl1">Commercial [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialMember" xlink:to="ions_CommercialMember_lbl1" xlink:title="label: CommercialMember to ions_CommercialMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CommercialMember_lbl2" xml:lang="en-US" id="ions_CommercialMember_lbl2">Commercial Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialMember" xlink:to="ions_CommercialMember_lbl2" xlink:title="label: CommercialMember to ions_CommercialMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_SpinrazaRoyaltiesMember" xlink:label="SpinrazaRoyaltiesMember" xlink:title="SpinrazaRoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaRoyaltiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SpinrazaRoyaltiesMember_lbl" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember_lbl">Royalty revenues from the sale of SPINRAZA (nusinersen).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaRoyaltiesMember" xlink:to="ions_SpinrazaRoyaltiesMember_lbl" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaRoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SpinrazaRoyaltiesMember_lbl1" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember_lbl1">Spinraza Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaRoyaltiesMember" xlink:to="ions_SpinrazaRoyaltiesMember_lbl1" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaRoyaltiesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SpinrazaRoyaltiesMember_lbl2" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember_lbl2">SPINRAZA Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaRoyaltiesMember" xlink:to="ions_SpinrazaRoyaltiesMember_lbl2" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_LicensingAndOtherRoyaltiesMember" xlink:label="LicensingAndOtherRoyaltiesMember" xlink:title="LicensingAndOtherRoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl">Revenue from license fees and other royalties, excluding royalties from the sale of SPINRAZA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicensingAndOtherRoyaltiesMember" xlink:to="ions_LicensingAndOtherRoyaltiesMember_lbl" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl1" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl1">Licensing and Other Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicensingAndOtherRoyaltiesMember" xlink:to="ions_LicensingAndOtherRoyaltiesMember_lbl1" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl2" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl2">Licensing and Other Royalty Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicensingAndOtherRoyaltiesMember" xlink:to="ions_LicensingAndOtherRoyaltiesMember_lbl2" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_CollaborativeAgreementRevenueMember" xlink:label="CollaborativeAgreementRevenueMember" xlink:title="CollaborativeAgreementRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeAgreementRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeAgreementRevenueMember_lbl" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember_lbl">Revenue from research and development services performed under a collaborative agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeAgreementRevenueMember" xlink:to="ions_CollaborativeAgreementRevenueMember_lbl" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeAgreementRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeAgreementRevenueMember_lbl1" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember_lbl1">Collaborative Agreement Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeAgreementRevenueMember" xlink:to="ions_CollaborativeAgreementRevenueMember_lbl1" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeAgreementRevenueMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeAgreementRevenueMember_lbl2" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember_lbl2">Collaborative Agreement Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeAgreementRevenueMember" xlink:to="ions_CollaborativeAgreementRevenueMember_lbl2" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NonCashCapitalAndPatentExpenditures" xlink:label="NonCashCapitalAndPatentExpenditures" xlink:title="NonCashCapitalAndPatentExpenditures" />
    <link:label xlink:type="resource" xlink:label="ions_NonCashCapitalAndPatentExpenditures_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NonCashCapitalAndPatentExpenditures_lbl" xml:lang="en-US" id="ions_NonCashCapitalAndPatentExpenditures_lbl">Future cash outflow to pay for purchases of fixed assets and patents that have been incurred.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonCashCapitalAndPatentExpenditures" xlink:to="ions_NonCashCapitalAndPatentExpenditures_lbl" xlink:title="label: NonCashCapitalAndPatentExpenditures to ions_NonCashCapitalAndPatentExpenditures_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NonCashCapitalAndPatentExpenditures_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NonCashCapitalAndPatentExpenditures_lbl1" xml:lang="en-US" id="ions_NonCashCapitalAndPatentExpenditures_lbl1">Non-cash Capital and Patent Expenditures</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonCashCapitalAndPatentExpenditures" xlink:to="ions_NonCashCapitalAndPatentExpenditures_lbl1" xlink:title="label: NonCashCapitalAndPatentExpenditures to ions_NonCashCapitalAndPatentExpenditures_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NonCashCapitalAndPatentExpenditures_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NonCashCapitalAndPatentExpenditures_lbl2" xml:lang="en-US" id="ions_NonCashCapitalAndPatentExpenditures_lbl2">Amounts accrued for capital and patent expenditures</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonCashCapitalAndPatentExpenditures" xlink:to="ions_NonCashCapitalAndPatentExpenditures_lbl2" xlink:title="label: NonCashCapitalAndPatentExpenditures to ions_NonCashCapitalAndPatentExpenditures_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1">Collaborative Arrangements and Licensing Agreements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsAbstract to ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_EquitySecuritiesPubliclyTradedCompaniesMember" xlink:label="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:title="EquitySecuritiesPubliclyTradedCompaniesMember" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl" xml:lang="en-US" id="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl">Ownership interest or right to acquire or dispose of ownership interest in publicly traded corporations and other legal entities for which ownership interest is represented by shares of common or preferred stock, convertible securities, stock rights, or stock warrants.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:to="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl" xlink:title="label: EquitySecuritiesPubliclyTradedCompaniesMember to ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1" xml:lang="en-US" id="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1">Equity Securities, Publicly Traded Companies [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:to="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1" xlink:title="label: EquitySecuritiesPubliclyTradedCompaniesMember to ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl2" xml:lang="en-US" id="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl2">Publicly Traded Equity Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:to="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl2" xlink:title="label: EquitySecuritiesPubliclyTradedCompaniesMember to ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" xlink:label="EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" xlink:title="EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl" xml:lang="en-US" id="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl">Accumulated amount of unrealized gain on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" xlink:to="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl" xlink:title="label: EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain to ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl1" xml:lang="en-US" id="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl1">Equity Securities, FV-NI, Accumulated Gross Unrealized Gain</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" xlink:to="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl1" xlink:title="label: EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain to ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl2" xml:lang="en-US" id="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl2">Gross unrealized gains</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" xlink:to="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl2" xlink:title="label: EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain to ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:label="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:title="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl" xml:lang="en-US" id="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl">Accumulated amount of unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:to="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl" xlink:title="label: EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss to ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl1" xml:lang="en-US" id="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl1">Equity Securities, FV-NI, Accumulated Gross Unrealized Loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:to="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl1" xlink:title="label: EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss to ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl2" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl2" xml:lang="en-US" id="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl2">Gross unrealized losses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:to="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl2" xlink:title="label: EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss to ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl">Total of (1) amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) cost of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl1" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl1">Debt Securities, Available-for-sale and Equity Securities, FV-NI, Cost</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl1" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl1">Debt Securities, Available-for-sale, Accumulated Gross Unrealized Gain, before Tax, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" xlink:to="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent to ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl2" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl2">Gross unrealized gains</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" xlink:to="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl2" xlink:title="label: DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent to ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_AstrazenecaCollaborationEplontersenMember" xlink:label="AstrazenecaCollaborationEplontersenMember" xlink:title="AstrazenecaCollaborationEplontersenMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationEplontersenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstrazenecaCollaborationEplontersenMember_lbl" xml:lang="en-US" id="ions_AstrazenecaCollaborationEplontersenMember_lbl">Collaboration agreement entered into with AstraZeneca PLC in December 2021 to develop and commercialize eplontersen. Eplontersen, formerly known as IONIS-TTR-L and AKCEA-TTR-L, is a ligand-conjugated (LICA) investigational antisense medicine designed to reduce the production of transthyretin, or TTR protein, to treat all types of TTR amyloidosis (ATTR), a systemic, progressive and fatal disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationEplontersenMember" xlink:to="ions_AstrazenecaCollaborationEplontersenMember_lbl" xlink:title="label: AstrazenecaCollaborationEplontersenMember to ions_AstrazenecaCollaborationEplontersenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationEplontersenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AstrazenecaCollaborationEplontersenMember_lbl1" xml:lang="en-US" id="ions_AstrazenecaCollaborationEplontersenMember_lbl1">AstraZeneca Collaboration, Eplontersen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationEplontersenMember" xlink:to="ions_AstrazenecaCollaborationEplontersenMember_lbl1" xlink:title="label: AstrazenecaCollaborationEplontersenMember to ions_AstrazenecaCollaborationEplontersenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationEplontersenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AstrazenecaCollaborationEplontersenMember_lbl2" xml:lang="en-US" id="ions_AstrazenecaCollaborationEplontersenMember_lbl2">Eplontersen Collaboration with AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationEplontersenMember" xlink:to="ions_AstrazenecaCollaborationEplontersenMember_lbl2" xlink:title="label: AstrazenecaCollaborationEplontersenMember to ions_AstrazenecaCollaborationEplontersenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NumberOfAgreementsWithCollaborationPartner" xlink:label="NumberOfAgreementsWithCollaborationPartner" xlink:title="NumberOfAgreementsWithCollaborationPartner" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAgreementsWithCollaborationPartner_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfAgreementsWithCollaborationPartner_lbl" xml:lang="en-US" id="ions_NumberOfAgreementsWithCollaborationPartner_lbl">The number of agreements entered into with the collaboration partner.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAgreementsWithCollaborationPartner" xlink:to="ions_NumberOfAgreementsWithCollaborationPartner_lbl" xlink:title="label: NumberOfAgreementsWithCollaborationPartner to ions_NumberOfAgreementsWithCollaborationPartner_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAgreementsWithCollaborationPartner_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfAgreementsWithCollaborationPartner_lbl1" xml:lang="en-US" id="ions_NumberOfAgreementsWithCollaborationPartner_lbl1">Number of agreements with collaboration partner</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAgreementsWithCollaborationPartner" xlink:to="ions_NumberOfAgreementsWithCollaborationPartner_lbl1" xlink:title="label: NumberOfAgreementsWithCollaborationPartner to ions_NumberOfAgreementsWithCollaborationPartner_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAgreementsWithCollaborationPartner_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfAgreementsWithCollaborationPartner_lbl2" xml:lang="en-US" id="ions_NumberOfAgreementsWithCollaborationPartner_lbl2">Number of agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAgreementsWithCollaborationPartner" xlink:to="ions_NumberOfAgreementsWithCollaborationPartner_lbl2" xlink:title="label: NumberOfAgreementsWithCollaborationPartner to ions_NumberOfAgreementsWithCollaborationPartner_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_UpfrontPaymentReceived" xlink:label="UpfrontPaymentReceived" xlink:title="UpfrontPaymentReceived" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontPaymentReceived_lbl" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl">The amount of upfront payments received during the period under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontPaymentReceived_lbl1" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl1">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl1" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpfrontPaymentReceived_lbl2" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl2">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl2" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_BiogenCollaboration2013StrategicNeurologyMember" xlink:label="BiogenCollaboration2013StrategicNeurologyMember" xlink:title="BiogenCollaboration2013StrategicNeurologyMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl">Collaborative agreement entered into with Biogen Inc. in September 2013 focused on applying antisense technology to advance the treatment of neurodegenerative diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1">Biogen Collaboration, 2013 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2">2013 Strategic Neurology Collaboration with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember" xlink:label="BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember" xlink:title="BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl" xml:lang="en-US" id="ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl">Collaborative agreements entered into with Biogen Inc. in (1) September 2013 focused on applying antisense technology to advance the treatment of neurodegenerative diseases (2013 Strategic Neurology Collaboration) and (2) December 2012 focused on developing and commercializing novel antisense drugs for up to three targets to treat neurological or neuromuscular diseases (2012 Neurology Collaboration).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember" xlink:to="ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl" xlink:title="label: BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember to ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl1">Biogen Collaborations, 2013 Strategic Neurology and 2012 Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember" xlink:to="ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl1" xlink:title="label: BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember to ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl2">Neurology Collaborations with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember" xlink:to="ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl2" xlink:title="label: BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember to ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_Ion859Member" xlink:label="Ion859Member" xlink:title="Ion859Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion859Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion859Member_lbl" xml:lang="en-US" id="ions_Ion859Member_lbl">ION859 (BIIB094) is an antisense medicine designed to inhibit the production of the Leucine Rich Repeat Kinase 2, or LRRK2, protein as a potential therapy for Parkinson's disease, or PD.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion859Member" xlink:to="ions_Ion859Member_lbl" xlink:title="label: Ion859Member to ions_Ion859Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion859Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion859Member_lbl1" xml:lang="en-US" id="ions_Ion859Member_lbl1">Ion859 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion859Member" xlink:to="ions_Ion859Member_lbl1" xlink:title="label: Ion859Member to ions_Ion859Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion859Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion859Member_lbl2" xml:lang="en-US" id="ions_Ion859Member_lbl2">ION859 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion859Member" xlink:to="ions_Ion859Member_lbl2" xlink:title="label: Ion859Member to ions_Ion859Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NumberOfTargetsAdvanced" xlink:label="NumberOfTargetsAdvanced" xlink:title="NumberOfTargetsAdvanced" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTargetsAdvanced_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfTargetsAdvanced_lbl" xml:lang="en-US" id="ions_NumberOfTargetsAdvanced_lbl">Number of targets advanced under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTargetsAdvanced" xlink:to="ions_NumberOfTargetsAdvanced_lbl" xlink:title="label: NumberOfTargetsAdvanced to ions_NumberOfTargetsAdvanced_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTargetsAdvanced_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfTargetsAdvanced_lbl1" xml:lang="en-US" id="ions_NumberOfTargetsAdvanced_lbl1">Number of targets advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTargetsAdvanced" xlink:to="ions_NumberOfTargetsAdvanced_lbl1" xlink:title="label: NumberOfTargetsAdvanced to ions_NumberOfTargetsAdvanced_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTargetsAdvanced_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfTargetsAdvanced_lbl2" xml:lang="en-US" id="ions_NumberOfTargetsAdvanced_lbl2">Number of targets advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTargetsAdvanced" xlink:to="ions_NumberOfTargetsAdvanced_lbl2" xlink:title="label: NumberOfTargetsAdvanced to ions_NumberOfTargetsAdvanced_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:label="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:title="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl">The number of separate performance obligations under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1">Revenue from Contract with Customer, Number of separate performance obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2">Number of separate performance obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_AlnylamCollaborationMember" xlink:label="AlnylamCollaborationMember" xlink:title="AlnylamCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AlnylamCollaborationMember_lbl" xml:lang="en-US" id="ions_AlnylamCollaborationMember_lbl">Collaboration agreement entered into with Alnylam Pharmaceuticals, Inc. in March 2004 to develop and commercialize RNAi therapeutics.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamCollaborationMember" xlink:to="ions_AlnylamCollaborationMember_lbl" xlink:title="label: AlnylamCollaborationMember to ions_AlnylamCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AlnylamCollaborationMember_lbl1" xml:lang="en-US" id="ions_AlnylamCollaborationMember_lbl1">Alnylam Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamCollaborationMember" xlink:to="ions_AlnylamCollaborationMember_lbl1" xlink:title="label: AlnylamCollaborationMember to ions_AlnylamCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamCollaborationMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AlnylamCollaborationMember_lbl2" xml:lang="en-US" id="ions_AlnylamCollaborationMember_lbl2">Alnylam [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamCollaborationMember" xlink:to="ions_AlnylamCollaborationMember_lbl2" xlink:title="label: AlnylamCollaborationMember to ions_AlnylamCollaborationMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NumberOfMaterialComponents" xlink:label="NumberOfMaterialComponents" xlink:title="NumberOfMaterialComponents" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMaterialComponents_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfMaterialComponents_lbl" xml:lang="en-US" id="ions_NumberOfMaterialComponents_lbl">The number of material components identified in the collaboration agreement under Accounting Standards Codification (ASC) 808, Collaborative Arrangements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMaterialComponents" xlink:to="ions_NumberOfMaterialComponents_lbl" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMaterialComponents_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfMaterialComponents_lbl1" xml:lang="en-US" id="ions_NumberOfMaterialComponents_lbl1">Number of material components</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMaterialComponents" xlink:to="ions_NumberOfMaterialComponents_lbl1" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMaterialComponents_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfMaterialComponents_lbl2" xml:lang="en-US" id="ions_NumberOfMaterialComponents_lbl2">Number of material components</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMaterialComponents" xlink:to="ions_NumberOfMaterialComponents_lbl2" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:label="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:title="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" xml:lang="en-US" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl">Percentage of costs associated with the ongoing global Phase 3 development program paid by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:to="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" xlink:title="label: PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner to ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" xml:lang="en-US" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1">Percentage of costs associated with ongoing global Phase 3 development program paid by Collaboration Partner</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:to="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" xlink:title="label: PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner to ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2" xml:lang="en-US" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2">Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:to="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2" xlink:title="label: PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner to ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:label="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:title="RevenueFromContractWithCustomerTransactionPriceAdditions" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl">The additional amount of consideration the Company earned under the collaboration agreement that is added to the transaction price.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:to="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl" xlink:title="label: RevenueFromContractWithCustomerTransactionPriceAdditions to ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1">Revenue from Contract with Customer, Transaction Price, Additions</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:to="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1" xlink:title="label: RevenueFromContractWithCustomerTransactionPriceAdditions to ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl2" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl2">Milestone payment received and added to transaction price</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:to="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl2" xlink:title="label: RevenueFromContractWithCustomerTransactionPriceAdditions to ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_BiogenIncMember" xlink:label="BiogenIncMember" xlink:title="BiogenIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenIncMember_lbl" xml:lang="en-US" id="ions_BiogenIncMember_lbl">Biogen Inc. is an American multinational biotechnology company.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenIncMember" xlink:to="ions_BiogenIncMember_lbl" xlink:title="label: BiogenIncMember to ions_BiogenIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenIncMember_lbl1" xml:lang="en-US" id="ions_BiogenIncMember_lbl1">Biogen Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenIncMember" xlink:to="ions_BiogenIncMember_lbl1" xlink:title="label: BiogenIncMember to ions_BiogenIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenIncMember_lbl2" xml:lang="en-US" id="ions_BiogenIncMember_lbl2">Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenIncMember" xlink:to="ions_BiogenIncMember_lbl2" xlink:title="label: BiogenIncMember to ions_BiogenIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:label="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:title="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" xml:lang="en-US" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl">Collaboration agreement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in October 2018 to develop IONIS-FB-L for the treatment of complement-mediated diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:to="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" xlink:title="label: RocheCollaborationIonisFbLForComplementMediatedDiseasesMember to ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" xml:lang="en-US" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1">Roche Collaboration, Ionis-Fb-L for Complement-Mediated Diseases [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:to="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" xlink:title="label: RocheCollaborationIonisFbLForComplementMediatedDiseasesMember to ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2" xml:lang="en-US" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2">Collaboration to Develop IONIS-FB-L with Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:to="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2" xlink:title="label: RocheCollaborationIonisFbLForComplementMediatedDiseasesMember to ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_RevenueFromContractWithCustomerTransactionPrice" xlink:label="RevenueFromContractWithCustomerTransactionPrice" xlink:title="RevenueFromContractWithCustomerTransactionPrice" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPrice_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice_lbl">The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice_lbl" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1">Revenue from Contract with Customer, Transaction Price</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2">Transaction price</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:label="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:title="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl" xml:lang="en-US" id="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl">Number of purchase and sale agreements entered into with a real estate investor.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:to="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl" xlink:title="label: NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor to ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1" xml:lang="en-US" id="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1">Number of purchase and sale agreements entered into with real estate investor</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:to="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1" xlink:title="label: NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor to ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl2" xml:lang="en-US" id="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl2">Number of purchase and sale agreements entered into with real estate investor</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:to="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl2" xlink:title="label: NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor to ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:label="LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:title="LesseeOperatingLeaseNumberOfOptionsToExtendLease" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl">The number of options to extend the lease under the lessee's operating leasing.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl" xlink:title="label: LesseeOperatingLeaseNumberOfOptionsToExtendLease to ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1">Lessee, Operating Lease, Number of options to extend lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xlink:title="label: LesseeOperatingLeaseNumberOfOptionsToExtendLease to ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl2">Number of options to extend lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl2" xlink:title="label: LesseeOperatingLeaseNumberOfOptionsToExtendLease to ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:label="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:title="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" />
    <link:label xlink:type="resource" xlink:label="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl" xml:lang="en-US" id="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl">Development chemistry and manufacturing facility located in Oceanside, California.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:to="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl" xlink:title="label: DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember to ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1" xml:lang="en-US" id="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1">Development Chemistry and Manufacturing Facility in Oceanside, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:to="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1" xlink:title="label: DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember to ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl2" xml:lang="en-US" id="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl2">Development Chemistry and Manufacturing Facility in Oceanside, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:to="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl2" xlink:title="label: DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember to ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_HeadquartersLocationInCarlsbadCaliforniaMember" xlink:label="HeadquartersLocationInCarlsbadCaliforniaMember" xlink:title="HeadquartersLocationInCarlsbadCaliforniaMember" />
    <link:label xlink:type="resource" xlink:label="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl" xml:lang="en-US" id="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl">Headquarters location located in Carlsbad, California.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="HeadquartersLocationInCarlsbadCaliforniaMember" xlink:to="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl" xlink:title="label: HeadquartersLocationInCarlsbadCaliforniaMember to ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1" xml:lang="en-US" id="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1">Headquarters Location in Carlsbad, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="HeadquartersLocationInCarlsbadCaliforniaMember" xlink:to="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1" xlink:title="label: HeadquartersLocationInCarlsbadCaliforniaMember to ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl2" xml:lang="en-US" id="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl2">Headquarters Location in Carlsbad, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="HeadquartersLocationInCarlsbadCaliforniaMember" xlink:to="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl2" xlink:title="label: HeadquartersLocationInCarlsbadCaliforniaMember to ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_OfficeSpaceInBostonMassachusettsMember" xlink:label="OfficeSpaceInBostonMassachusettsMember" xlink:title="OfficeSpaceInBostonMassachusettsMember" />
    <link:label xlink:type="resource" xlink:label="ions_OfficeSpaceInBostonMassachusettsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OfficeSpaceInBostonMassachusettsMember_lbl" xml:lang="en-US" id="ions_OfficeSpaceInBostonMassachusettsMember_lbl">Office space located in Boston, Massachusetts.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OfficeSpaceInBostonMassachusettsMember" xlink:to="ions_OfficeSpaceInBostonMassachusettsMember_lbl" xlink:title="label: OfficeSpaceInBostonMassachusettsMember to ions_OfficeSpaceInBostonMassachusettsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OfficeSpaceInBostonMassachusettsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OfficeSpaceInBostonMassachusettsMember_lbl1" xml:lang="en-US" id="ions_OfficeSpaceInBostonMassachusettsMember_lbl1">Office Space in Boston, Massachusetts [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OfficeSpaceInBostonMassachusettsMember" xlink:to="ions_OfficeSpaceInBostonMassachusettsMember_lbl1" xlink:title="label: OfficeSpaceInBostonMassachusettsMember to ions_OfficeSpaceInBostonMassachusettsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OfficeSpaceInBostonMassachusettsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OfficeSpaceInBostonMassachusettsMember_lbl2" xml:lang="en-US" id="ions_OfficeSpaceInBostonMassachusettsMember_lbl2">Office Space in Boston, Massachusetts [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OfficeSpaceInBostonMassachusettsMember" xlink:to="ions_OfficeSpaceInBostonMassachusettsMember_lbl2" xlink:title="label: OfficeSpaceInBostonMassachusettsMember to ions_OfficeSpaceInBostonMassachusettsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_LessorOperatingLeaseFreeRentPeriod" xlink:label="LessorOperatingLeaseFreeRentPeriod" xlink:title="LessorOperatingLeaseFreeRentPeriod" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeaseFreeRentPeriod_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LessorOperatingLeaseFreeRentPeriod_lbl" xml:lang="en-US" id="ions_LessorOperatingLeaseFreeRentPeriod_lbl">Period of time lessor will provide free rent under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeaseFreeRentPeriod" xlink:to="ions_LessorOperatingLeaseFreeRentPeriod_lbl" xlink:title="label: LessorOperatingLeaseFreeRentPeriod to ions_LessorOperatingLeaseFreeRentPeriod_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeaseFreeRentPeriod_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LessorOperatingLeaseFreeRentPeriod_lbl1" xml:lang="en-US" id="ions_LessorOperatingLeaseFreeRentPeriod_lbl1">Lessor, Operating Lease, Free Rent Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeaseFreeRentPeriod" xlink:to="ions_LessorOperatingLeaseFreeRentPeriod_lbl1" xlink:title="label: LessorOperatingLeaseFreeRentPeriod to ions_LessorOperatingLeaseFreeRentPeriod_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeaseFreeRentPeriod_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LessorOperatingLeaseFreeRentPeriod_lbl2" xml:lang="en-US" id="ions_LessorOperatingLeaseFreeRentPeriod_lbl2">Free rent period under sublease agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeaseFreeRentPeriod" xlink:to="ions_LessorOperatingLeaseFreeRentPeriod_lbl2" xlink:title="label: LessorOperatingLeaseFreeRentPeriod to ions_LessorOperatingLeaseFreeRentPeriod_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" xlink:label="NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" xlink:title="NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl" xml:lang="en-US" id="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl">Number of lots of undeveloped land adjacent to the Company's headquarters in Carlsbad, California included in purchase and sale agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" xlink:to="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl" xlink:title="label: NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement to ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl1" xml:lang="en-US" id="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl1">Number of lots of undeveloped land included in purchase and sale agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" xlink:to="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl1" xlink:title="label: NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement to ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_ConvertibleSeniorNotes1PercentMember" xlink:label="ConvertibleSeniorNotes1PercentMember" xlink:title="ConvertibleSeniorNotes1PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl">1 percent convertible senior notes due November 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl1">Convertible Senior Notes 1 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl2">1 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl3">1% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_CumulativePaymentsReceived" xlink:label="CumulativePaymentsReceived" xlink:title="CumulativePaymentsReceived" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CumulativePaymentsReceived_lbl" xml:lang="en-US" id="ions_CumulativePaymentsReceived_lbl">Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsReceived" xlink:to="ions_CumulativePaymentsReceived_lbl" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CumulativePaymentsReceived_lbl1" xml:lang="en-US" id="ions_CumulativePaymentsReceived_lbl1">Cumulative payments received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsReceived" xlink:to="ions_CumulativePaymentsReceived_lbl1" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CumulativePaymentsReceived_lbl2" xml:lang="en-US" id="ions_CumulativePaymentsReceived_lbl2">Cumulative payments received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsReceived" xlink:to="ions_CumulativePaymentsReceived_lbl2" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1">Collaborative Arrangement and Licensing Agreement [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAbstract to ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_BayerCollaborationIonisFxiMember" xlink:label="BayerCollaborationIonisFxiMember" xlink:title="BayerCollaborationIonisFxiMember" />
    <link:label xlink:type="resource" xlink:label="ions_BayerCollaborationIonisFxiMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BayerCollaborationIonisFxiMember_lbl" xml:lang="en-US" id="ions_BayerCollaborationIonisFxiMember_lbl">Collaboration agreement entered into with Bayer HealthCare in May 2015 to develop and commercialize IONIS-FXI for the prevention of thrombosis.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BayerCollaborationIonisFxiMember" xlink:to="ions_BayerCollaborationIonisFxiMember_lbl" xlink:title="label: BayerCollaborationIonisFxiMember to ions_BayerCollaborationIonisFxiMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BayerCollaborationIonisFxiMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BayerCollaborationIonisFxiMember_lbl1" xml:lang="en-US" id="ions_BayerCollaborationIonisFxiMember_lbl1">Bayer Collaboration, Ionis-Fxi [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BayerCollaborationIonisFxiMember" xlink:to="ions_BayerCollaborationIonisFxiMember_lbl1" xlink:title="label: BayerCollaborationIonisFxiMember to ions_BayerCollaborationIonisFxiMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BayerCollaborationIonisFxiMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BayerCollaborationIonisFxiMember_lbl2" xml:lang="en-US" id="ions_BayerCollaborationIonisFxiMember_lbl2">Bayer Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BayerCollaborationIonisFxiMember" xlink:to="ions_BayerCollaborationIonisFxiMember_lbl2" xlink:title="label: BayerCollaborationIonisFxiMember to ions_BayerCollaborationIonisFxiMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_ClinicalRawMaterialsMember" xlink:label="ClinicalRawMaterialsMember" xlink:title="ClinicalRawMaterialsMember" />
    <link:label xlink:type="resource" xlink:label="ions_ClinicalRawMaterialsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ClinicalRawMaterialsMember_lbl" xml:lang="en-US" id="ions_ClinicalRawMaterialsMember_lbl">Raw materials purchased for use in producing medicines that have alternative future uses until they are used.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ClinicalRawMaterialsMember" xlink:to="ions_ClinicalRawMaterialsMember_lbl" xlink:title="label: ClinicalRawMaterialsMember to ions_ClinicalRawMaterialsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ClinicalRawMaterialsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ClinicalRawMaterialsMember_lbl1" xml:lang="en-US" id="ions_ClinicalRawMaterialsMember_lbl1">Clinical Raw Materials [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ClinicalRawMaterialsMember" xlink:to="ions_ClinicalRawMaterialsMember_lbl1" xlink:title="label: ClinicalRawMaterialsMember to ions_ClinicalRawMaterialsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ClinicalRawMaterialsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ClinicalRawMaterialsMember_lbl2" xml:lang="en-US" id="ions_ClinicalRawMaterialsMember_lbl2">Clinical [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ClinicalRawMaterialsMember" xlink:to="ions_ClinicalRawMaterialsMember_lbl2" xlink:title="label: ClinicalRawMaterialsMember to ions_ClinicalRawMaterialsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_CommercialRawMaterialsMember" xlink:label="CommercialRawMaterialsMember" xlink:title="CommercialRawMaterialsMember" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialRawMaterialsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CommercialRawMaterialsMember_lbl" xml:lang="en-US" id="ions_CommercialRawMaterialsMember_lbl">Raw materials purchased for manufacturing medicines for commercial production.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialRawMaterialsMember" xlink:to="ions_CommercialRawMaterialsMember_lbl" xlink:title="label: CommercialRawMaterialsMember to ions_CommercialRawMaterialsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialRawMaterialsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CommercialRawMaterialsMember_lbl1" xml:lang="en-US" id="ions_CommercialRawMaterialsMember_lbl1">Commercial Raw Materials [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialRawMaterialsMember" xlink:to="ions_CommercialRawMaterialsMember_lbl1" xlink:title="label: CommercialRawMaterialsMember to ions_CommercialRawMaterialsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialRawMaterialsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CommercialRawMaterialsMember_lbl2" xml:lang="en-US" id="ions_CommercialRawMaterialsMember_lbl2">Commercial [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialRawMaterialsMember" xlink:to="ions_CommercialRawMaterialsMember_lbl2" xlink:title="label: CommercialRawMaterialsMember to ions_CommercialRawMaterialsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_AccruedInLicensingFeesCurrent" xlink:label="AccruedInLicensingFeesCurrent" xlink:title="AccruedInLicensingFeesCurrent" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedInLicensingFeesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedInLicensingFeesCurrent_lbl" xml:lang="en-US" id="ions_AccruedInLicensingFeesCurrent_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for in-licensing fees under collaboration agreements. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedInLicensingFeesCurrent" xlink:to="ions_AccruedInLicensingFeesCurrent_lbl" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedInLicensingFeesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedInLicensingFeesCurrent_lbl1" xml:lang="en-US" id="ions_AccruedInLicensingFeesCurrent_lbl1">Accrued in-licensing fees, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedInLicensingFeesCurrent" xlink:to="ions_AccruedInLicensingFeesCurrent_lbl1" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedInLicensingFeesCurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedInLicensingFeesCurrent_lbl2" xml:lang="en-US" id="ions_AccruedInLicensingFeesCurrent_lbl2">In-licensing expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedInLicensingFeesCurrent" xlink:to="ions_AccruedInLicensingFeesCurrent_lbl2" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_AccruedCommercialExpensesCurrent" xlink:label="AccruedCommercialExpensesCurrent" xlink:title="AccruedCommercialExpensesCurrent" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedCommercialExpensesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedCommercialExpensesCurrent_lbl" xml:lang="en-US" id="ions_AccruedCommercialExpensesCurrent_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for commercial expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedCommercialExpensesCurrent" xlink:to="ions_AccruedCommercialExpensesCurrent_lbl" xlink:title="label: AccruedCommercialExpensesCurrent to ions_AccruedCommercialExpensesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedCommercialExpensesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedCommercialExpensesCurrent_lbl1" xml:lang="en-US" id="ions_AccruedCommercialExpensesCurrent_lbl1">Accrued commercial expenses, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedCommercialExpensesCurrent" xlink:to="ions_AccruedCommercialExpensesCurrent_lbl1" xlink:title="label: AccruedCommercialExpensesCurrent to ions_AccruedCommercialExpensesCurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedCommercialExpensesCurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedCommercialExpensesCurrent_lbl2" xml:lang="en-US" id="ions_AccruedCommercialExpensesCurrent_lbl2">Commercial expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedCommercialExpensesCurrent" xlink:to="ions_AccruedCommercialExpensesCurrent_lbl2" xlink:title="label: AccruedCommercialExpensesCurrent to ions_AccruedCommercialExpensesCurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_AccruedClinicalDevelopmentExpenses" xlink:label="AccruedClinicalDevelopmentExpenses" xlink:title="AccruedClinicalDevelopmentExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalDevelopmentExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedClinicalDevelopmentExpenses_lbl" xml:lang="en-US" id="ions_AccruedClinicalDevelopmentExpenses_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for clinical development expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalDevelopmentExpenses" xlink:to="ions_AccruedClinicalDevelopmentExpenses_lbl" xlink:title="label: AccruedClinicalDevelopmentExpenses to ions_AccruedClinicalDevelopmentExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalDevelopmentExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedClinicalDevelopmentExpenses_lbl1" xml:lang="en-US" id="ions_AccruedClinicalDevelopmentExpenses_lbl1">Accrued clinical development expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalDevelopmentExpenses" xlink:to="ions_AccruedClinicalDevelopmentExpenses_lbl1" xlink:title="label: AccruedClinicalDevelopmentExpenses to ions_AccruedClinicalDevelopmentExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalDevelopmentExpenses_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedClinicalDevelopmentExpenses_lbl2" xml:lang="en-US" id="ions_AccruedClinicalDevelopmentExpenses_lbl2">Clinical development expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalDevelopmentExpenses" xlink:to="ions_AccruedClinicalDevelopmentExpenses_lbl2" xlink:title="label: AccruedClinicalDevelopmentExpenses to ions_AccruedClinicalDevelopmentExpenses_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NumberOfCollaborationAgreements" xlink:label="NumberOfCollaborationAgreements" xlink:title="NumberOfCollaborationAgreements" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCollaborationAgreements_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfCollaborationAgreements_lbl" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements_lbl">The number of collaboration agreements with the collaboration partner.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCollaborationAgreements" xlink:to="ions_NumberOfCollaborationAgreements_lbl" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCollaborationAgreements_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfCollaborationAgreements_lbl1" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements_lbl1">Number of collaboration agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCollaborationAgreements" xlink:to="ions_NumberOfCollaborationAgreements_lbl1" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCollaborationAgreements_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfCollaborationAgreements_lbl2" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements_lbl2">Number of collaboration agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCollaborationAgreements" xlink:to="ions_NumberOfCollaborationAgreements_lbl2" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl">The maximum amount of payments receivable for development milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1">Maximum amount of payments receivable for development milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2">Maximum amount of payments receivable for development milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl">The maximum amount of payments receivable for regulatory milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1">Maximum amount of payments receivable for regulatory milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2">Maximum amount of payments receivable for regulatory milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:label="RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:title="RoyaltyPercentageReceivedOnNetSalesOfMedicine" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl">Royalty percentage received on the net sales of a medicine by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfMedicine to ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1">Royalty percentage received on net sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfMedicine to ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl2" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl2">Royalty percentage received on net sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfMedicine to ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl">The maximum amount of payments receivable for sales-related milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones to ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl1">Maximum amount of payments receivable for sales-related milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones to ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl2">Maximum amount of payments receivable for sales-related milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones to ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_RocheCollaborationHuntingtonsDiseaseMember" xlink:label="RocheCollaborationHuntingtonsDiseaseMember" xlink:title="RocheCollaborationHuntingtonsDiseaseMember" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl" xml:lang="en-US" id="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl">Collaboration agreement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in April 2013 to develop treatments for Huntington's disease, or HD, based on the Company's antisense technology.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationHuntingtonsDiseaseMember" xlink:to="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl" xlink:title="label: RocheCollaborationHuntingtonsDiseaseMember to ions_RocheCollaborationHuntingtonsDiseaseMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1" xml:lang="en-US" id="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1">Roche Collaboration, Huntington's Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationHuntingtonsDiseaseMember" xlink:to="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1" xlink:title="label: RocheCollaborationHuntingtonsDiseaseMember to ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl2" xml:lang="en-US" id="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl2">Collaboration to Develop Treatments for Huntington's Disease with Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationHuntingtonsDiseaseMember" xlink:to="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl2" xlink:title="label: RocheCollaborationHuntingtonsDiseaseMember to ions_RocheCollaborationHuntingtonsDiseaseMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NumberOfDiseaseIndications" xlink:label="NumberOfDiseaseIndications" xlink:title="NumberOfDiseaseIndications" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDiseaseIndications_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfDiseaseIndications_lbl" xml:lang="en-US" id="ions_NumberOfDiseaseIndications_lbl">Number of disease indications for which studies are currently being conducted under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDiseaseIndications" xlink:to="ions_NumberOfDiseaseIndications_lbl" xlink:title="label: NumberOfDiseaseIndications to ions_NumberOfDiseaseIndications_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDiseaseIndications_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfDiseaseIndications_lbl1" xml:lang="en-US" id="ions_NumberOfDiseaseIndications_lbl1">Number of disease indications</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDiseaseIndications" xlink:to="ions_NumberOfDiseaseIndications_lbl1" xlink:title="label: NumberOfDiseaseIndications to ions_NumberOfDiseaseIndications_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDiseaseIndications_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfDiseaseIndications_lbl2" xml:lang="en-US" id="ions_NumberOfDiseaseIndications_lbl2">Number of disease indications</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDiseaseIndications" xlink:to="ions_NumberOfDiseaseIndications_lbl2" xlink:title="label: NumberOfDiseaseIndications to ions_NumberOfDiseaseIndications_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NextPotentialMilestonePayment" xlink:label="NextPotentialMilestonePayment" xlink:title="NextPotentialMilestonePayment" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialMilestonePayment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NextPotentialMilestonePayment_lbl" xml:lang="en-US" id="ions_NextPotentialMilestonePayment_lbl">The next potential milestone payment to be earned under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialMilestonePayment" xlink:to="ions_NextPotentialMilestonePayment_lbl" xlink:title="label: NextPotentialMilestonePayment to ions_NextPotentialMilestonePayment_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialMilestonePayment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NextPotentialMilestonePayment_lbl1" xml:lang="en-US" id="ions_NextPotentialMilestonePayment_lbl1">Next potential milestone payment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialMilestonePayment" xlink:to="ions_NextPotentialMilestonePayment_lbl1" xlink:title="label: NextPotentialMilestonePayment to ions_NextPotentialMilestonePayment_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialMilestonePayment_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NextPotentialMilestonePayment_lbl2" xml:lang="en-US" id="ions_NextPotentialMilestonePayment_lbl2">Next prospective milestone</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialMilestonePayment" xlink:to="ions_NextPotentialMilestonePayment_lbl2" xlink:title="label: NextPotentialMilestonePayment to ions_NextPotentialMilestonePayment_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_RocheCollaborationsMember" xlink:label="RocheCollaborationsMember" xlink:title="RocheCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RocheCollaborationsMember_lbl" xml:lang="en-US" id="ions_RocheCollaborationsMember_lbl">Collaboration agreements entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationsMember" xlink:to="ions_RocheCollaborationsMember_lbl" xlink:title="label: RocheCollaborationsMember to ions_RocheCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RocheCollaborationsMember_lbl1" xml:lang="en-US" id="ions_RocheCollaborationsMember_lbl1">Roche Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationsMember" xlink:to="ions_RocheCollaborationsMember_lbl1" xlink:title="label: RocheCollaborationsMember to ions_RocheCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_RocheCollaborationsMember_lbl2" xml:lang="en-US" id="ions_RocheCollaborationsMember_lbl2">Roche Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationsMember" xlink:to="ions_RocheCollaborationsMember_lbl2" xlink:title="label: RocheCollaborationsMember to ions_RocheCollaborationsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_ImmunoglobulinANephropathyMember" xlink:label="ImmunoglobulinANephropathyMember" xlink:title="ImmunoglobulinANephropathyMember" />
    <link:label xlink:type="resource" xlink:label="ions_ImmunoglobulinANephropathyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ImmunoglobulinANephropathyMember_lbl" xml:lang="en-US" id="ions_ImmunoglobulinANephropathyMember_lbl">Immunoglobulin A nephropathy (IgAN) is a chronic kidney disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ImmunoglobulinANephropathyMember" xlink:to="ions_ImmunoglobulinANephropathyMember_lbl" xlink:title="label: ImmunoglobulinANephropathyMember to ions_ImmunoglobulinANephropathyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ImmunoglobulinANephropathyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ImmunoglobulinANephropathyMember_lbl1" xml:lang="en-US" id="ions_ImmunoglobulinANephropathyMember_lbl1">Immunoglobulin A Nephropathy [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ImmunoglobulinANephropathyMember" xlink:to="ions_ImmunoglobulinANephropathyMember_lbl1" xlink:title="label: ImmunoglobulinANephropathyMember to ions_ImmunoglobulinANephropathyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ImmunoglobulinANephropathyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ImmunoglobulinANephropathyMember_lbl2" xml:lang="en-US" id="ions_ImmunoglobulinANephropathyMember_lbl2">IgAN [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ImmunoglobulinANephropathyMember" xlink:to="ions_ImmunoglobulinANephropathyMember_lbl2" xlink:title="label: ImmunoglobulinANephropathyMember to ions_ImmunoglobulinANephropathyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_GeographicAtrophyMember" xlink:label="GeographicAtrophyMember" xlink:title="GeographicAtrophyMember" />
    <link:label xlink:type="resource" xlink:label="ions_GeographicAtrophyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GeographicAtrophyMember_lbl" xml:lang="en-US" id="ions_GeographicAtrophyMember_lbl">Geographic Atrophy (GA) is the advanced stage of advanced aged-related macular degeneration (AMD).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GeographicAtrophyMember" xlink:to="ions_GeographicAtrophyMember_lbl" xlink:title="label: GeographicAtrophyMember to ions_GeographicAtrophyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_GeographicAtrophyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GeographicAtrophyMember_lbl1" xml:lang="en-US" id="ions_GeographicAtrophyMember_lbl1">Geographic Atrophy [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GeographicAtrophyMember" xlink:to="ions_GeographicAtrophyMember_lbl1" xlink:title="label: GeographicAtrophyMember to ions_GeographicAtrophyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GeographicAtrophyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GeographicAtrophyMember_lbl2" xml:lang="en-US" id="ions_GeographicAtrophyMember_lbl2">GA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GeographicAtrophyMember" xlink:to="ions_GeographicAtrophyMember_lbl2" xlink:title="label: GeographicAtrophyMember to ions_GeographicAtrophyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NextPotentialPayment" xlink:label="NextPotentialPayment" xlink:title="NextPotentialPayment" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialPayment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NextPotentialPayment_lbl" xml:lang="en-US" id="ions_NextPotentialPayment_lbl">The next potential payment to be earned under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialPayment" xlink:to="ions_NextPotentialPayment_lbl" xlink:title="label: NextPotentialPayment to ions_NextPotentialPayment_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialPayment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NextPotentialPayment_lbl1" xml:lang="en-US" id="ions_NextPotentialPayment_lbl1">Next potential payment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialPayment" xlink:to="ions_NextPotentialPayment_lbl1" xlink:title="label: NextPotentialPayment to ions_NextPotentialPayment_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialPayment_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NextPotentialPayment_lbl2" xml:lang="en-US" id="ions_NextPotentialPayment_lbl2">Next prospective payment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialPayment" xlink:to="ions_NextPotentialPayment_lbl2" xlink:title="label: NextPotentialPayment to ions_NextPotentialPayment_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NumberOfMilestonePaymentsRecognizedInFull" xlink:label="NumberOfMilestonePaymentsRecognizedInFull" xlink:title="NumberOfMilestonePaymentsRecognizedInFull" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMilestonePaymentsRecognizedInFull_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfMilestonePaymentsRecognizedInFull_lbl" xml:lang="en-US" id="ions_NumberOfMilestonePaymentsRecognizedInFull_lbl">Number of milestone payments recognized in full during the period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMilestonePaymentsRecognizedInFull" xlink:to="ions_NumberOfMilestonePaymentsRecognizedInFull_lbl" xlink:title="label: NumberOfMilestonePaymentsRecognizedInFull to ions_NumberOfMilestonePaymentsRecognizedInFull_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMilestonePaymentsRecognizedInFull_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfMilestonePaymentsRecognizedInFull_lbl1" xml:lang="en-US" id="ions_NumberOfMilestonePaymentsRecognizedInFull_lbl1">Number of milestone payments recognized in full</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMilestonePaymentsRecognizedInFull" xlink:to="ions_NumberOfMilestonePaymentsRecognizedInFull_lbl1" xlink:title="label: NumberOfMilestonePaymentsRecognizedInFull to ions_NumberOfMilestonePaymentsRecognizedInFull_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMilestonePaymentsRecognizedInFull_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfMilestonePaymentsRecognizedInFull_lbl2" xml:lang="en-US" id="ions_NumberOfMilestonePaymentsRecognizedInFull_lbl2">Number of milestone payments recognized in full</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMilestonePaymentsRecognizedInFull" xlink:to="ions_NumberOfMilestonePaymentsRecognizedInFull_lbl2" xlink:title="label: NumberOfMilestonePaymentsRecognizedInFull to ions_NumberOfMilestonePaymentsRecognizedInFull_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_BiogenCollaborationsMember" xlink:label="BiogenCollaborationsMember" xlink:title="BiogenCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaborationsMember_lbl" xml:lang="en-US" id="ions_BiogenCollaborationsMember_lbl">Collaboration agreements entered into with Biogen Inc.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationsMember" xlink:to="ions_BiogenCollaborationsMember_lbl" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaborationsMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaborationsMember_lbl1">Biogen Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationsMember" xlink:to="ions_BiogenCollaborationsMember_lbl1" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_BiogenCollaborationsMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaborationsMember_lbl2">Biogen Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationsMember" xlink:to="ions_BiogenCollaborationsMember_lbl2" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl">Disclosure of information about collaborative arrangements and non-collaborative arrangement transactions.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1">Collaborative Arrangements and Non-collaborative Arrangement Transactions Disclosure [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl">Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1">Collaborative Arrangements and Non-collaborative Arrangement Transactions Disclosure [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2">Collaborative Arrangements and Licensing Agreements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_PeriodAfterBillingWhenPaymentIsReceived" xlink:label="PeriodAfterBillingWhenPaymentIsReceived" xlink:title="PeriodAfterBillingWhenPaymentIsReceived" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" xml:lang="en-US" id="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl">The time period between billing a collaboration partner for goods delivered or services performed that are due unconditionally and payment is received from the collaboration partner, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterBillingWhenPaymentIsReceived" xlink:to="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" xlink:title="label: PeriodAfterBillingWhenPaymentIsReceived to ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" xml:lang="en-US" id="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1">Period after billing when payment is received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterBillingWhenPaymentIsReceived" xlink:to="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" xlink:title="label: PeriodAfterBillingWhenPaymentIsReceived to ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" xml:lang="en-US" id="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2">Period of time after billing when payment is received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterBillingWhenPaymentIsReceived" xlink:to="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" xlink:title="label: PeriodAfterBillingWhenPaymentIsReceived to ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_SignificantPartnersAbstract" xlink:label="SignificantPartnersAbstract" xlink:title="SignificantPartnersAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_SignificantPartnersAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SignificantPartnersAbstract_lbl1" xml:lang="en-US" id="ions_SignificantPartnersAbstract_lbl1">Significant Partners [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantPartnersAbstract" xlink:to="ions_SignificantPartnersAbstract_lbl1" xlink:title="label: SignificantPartnersAbstract to ions_SignificantPartnersAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_NumberOfSignificantCustomers" xlink:label="NumberOfSignificantCustomers" xlink:title="NumberOfSignificantCustomers" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantCustomers_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfSignificantCustomers_lbl" xml:lang="en-US" id="ions_NumberOfSignificantCustomers_lbl">The number of significant customers with which the Company does business.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantCustomers" xlink:to="ions_NumberOfSignificantCustomers_lbl" xlink:title="label: NumberOfSignificantCustomers to ions_NumberOfSignificantCustomers_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantCustomers_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfSignificantCustomers_lbl1" xml:lang="en-US" id="ions_NumberOfSignificantCustomers_lbl1">Number of Significant Customers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantCustomers" xlink:to="ions_NumberOfSignificantCustomers_lbl1" xlink:title="label: NumberOfSignificantCustomers to ions_NumberOfSignificantCustomers_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantCustomers_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfSignificantCustomers_lbl2" xml:lang="en-US" id="ions_NumberOfSignificantCustomers_lbl2">Number of significant customers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantCustomers" xlink:to="ions_NumberOfSignificantCustomers_lbl2" xlink:title="label: NumberOfSignificantCustomers to ions_NumberOfSignificantCustomers_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_TwoSignificantCustomersMember" xlink:label="TwoSignificantCustomersMember" xlink:title="TwoSignificantCustomersMember" />
    <link:label xlink:type="resource" xlink:label="ions_TwoSignificantCustomersMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TwoSignificantCustomersMember_lbl" xml:lang="en-US" id="ions_TwoSignificantCustomersMember_lbl">Two significant corporate partners and leading global pharmaceutical companies that are working alongside the Company to develop the Company's drugs, advance the Company's technology, and prepare to commercialize and sell the Company's drugs under collaborative arrangement and licensing agreements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TwoSignificantCustomersMember" xlink:to="ions_TwoSignificantCustomersMember_lbl" xlink:title="label: TwoSignificantCustomersMember to ions_TwoSignificantCustomersMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TwoSignificantCustomersMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TwoSignificantCustomersMember_lbl1" xml:lang="en-US" id="ions_TwoSignificantCustomersMember_lbl1">Two Significant Customers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TwoSignificantCustomersMember" xlink:to="ions_TwoSignificantCustomersMember_lbl1" xlink:title="label: TwoSignificantCustomersMember to ions_TwoSignificantCustomersMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TwoSignificantCustomersMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TwoSignificantCustomersMember_lbl2" xml:lang="en-US" id="ions_TwoSignificantCustomersMember_lbl2">Two Significant Customers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TwoSignificantCustomersMember" xlink:to="ions_TwoSignificantCustomersMember_lbl2" xlink:title="label: TwoSignificantCustomersMember to ions_TwoSignificantCustomersMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_ThreeSignificantCustomersMember" xlink:label="ThreeSignificantCustomersMember" xlink:title="ThreeSignificantCustomersMember" />
    <link:label xlink:type="resource" xlink:label="ions_ThreeSignificantCustomersMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ThreeSignificantCustomersMember_lbl" xml:lang="en-US" id="ions_ThreeSignificantCustomersMember_lbl">Three significant corporate partners and leading global pharmaceutical companies that are working alongside the Company to develop the Company's drugs, advance the Company's technology, and prepare to commercialize and sell the Company's drugs under collaborative arrangement and licensing agreements.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:label="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:title="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl">The computed conversion price per share of the debt instrument based on the the conversion feature embedded in the debt instrument and the impact of the purchased hedges in the call spread transaction.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20220930.xsd#ions_CallSpread" xlink:label="CallSpread" xlink:title="CallSpread" />
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<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592582572448">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Document and Entity Information - shares<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Nov. 03, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_CoverAbstract', window );"><strong>Cover [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentType', window );">Document Type</a></td>
<td class="text">10-Q<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_AmendmentFlag', window );">Amendment Flag</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentQuarterlyReport', window );">Document Quarterly Report</a></td>
<td class="text">true<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentPeriodEndDate', window );">Document Period End Date</a></td>
<td class="text">Sep. 30,  2022<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_CurrentFiscalYearEndDate', window );">Current Fiscal Year End Date</a></td>
<td class="text">--12-31<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentFiscalYearFocus', window );">Document Fiscal Year Focus</a></td>
<td class="text">2022<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentFiscalPeriodFocus', window );">Document Fiscal Period Focus</a></td>
<td class="text">Q3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentTransitionReport', window );">Document Transition Report</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityFileNumber', window );">Entity File Number</a></td>
<td class="text">000-19125<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityRegistrantName', window );">Entity Registrant Name</a></td>
<td class="text">Ionis Pharmaceuticals, Inc.<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityCentralIndexKey', window );">Entity Central Index Key</a></td>
<td class="text">0000874015<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityIncorporationStateCountryCode', window );">Entity Incorporation, State or Country Code</a></td>
<td class="text">DE<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityTaxIdentificationNumber', window );">Entity Tax Identification Number</a></td>
<td class="text">33-0336973<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressAddressLine1', window );">Entity Address, Address Line One</a></td>
<td class="text">2855 Gazelle Court<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressCityOrTown', window );">Entity Address, City or Town</a></td>
<td class="text">Carlsbad<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressStateOrProvince', window );">Entity Address, State or Province</a></td>
<td class="text">CA<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressPostalZipCode', window );">Entity Address, Postal Zip Code</a></td>
<td class="text">92010<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_CityAreaCode', window );">City Area Code</a></td>
<td class="text">760<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_LocalPhoneNumber', window );">Local Phone Number</a></td>
<td class="text">931-9200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_Security12bTitle', window );">Title of 12(b) Security</a></td>
<td class="text">Common Stock, $.001 Par Value<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_TradingSymbol', window );">Trading Symbol</a></td>
<td class="text">IONS<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_SecurityExchangeName', window );">Security Exchange Name</a></td>
<td class="text">NASDAQ<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityCurrentReportingStatus', window );">Entity Current Reporting Status</a></td>
<td class="text">Yes<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityInteractiveDataCurrent', window );">Entity Interactive Data Current</a></td>
<td class="text">Yes<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityFilerCategory', window );">Entity Filer Category</a></td>
<td class="text">Large Accelerated Filer<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntitySmallBusiness', window );">Entity Small Business</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityEmergingGrowthCompany', window );">Entity Emerging Growth Company</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityShellCompany', window );">Entity Shell Company</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityCommonStockSharesOutstanding', window );">Entity Common Stock, Shares Outstanding</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">142,050,336<span></span>
</td>
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<div style="display: none;">
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the XBRL content amends previously-filed or accepted submission.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_AmendmentFlag</td>
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<td>xbrli:booleanItemType</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CityAreaCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Area code of city</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CityAreaCode</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td>xbrli:normalizedStringItemType</td>
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<td>na</td>
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<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CoverAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cover page.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CoverAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CurrentFiscalYearEndDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>End date of current fiscal year in the format --MM-DD.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CurrentFiscalYearEndDate</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td>xbrli:gMonthDayItemType</td>
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<td>na</td>
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<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentFiscalPeriodFocus">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Fiscal period values are FY, Q1, Q2, and Q3.  1st, 2nd and 3rd quarter 10-Q or 10-QT statements have value Q1, Q2, and Q3 respectively, with 10-K, 10-KT or other fiscal year statements having FY.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentFiscalPeriodFocus</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td><strong> Data Type:</strong></td>
<td>dei:fiscalPeriodItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentFiscalYearFocus">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>This is focus fiscal year of the document report in YYYY format. For a 2006 annual report, which may also provide financial information from prior periods, fiscal 2006 should be given as the fiscal year focus. Example: 2006.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentFiscalYearFocus</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:gYearItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentPeriodEndDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For the EDGAR submission types of Form 8-K: the date of the report, the date of the earliest event reported; for the EDGAR submission types of Form N-1A: the filing date; for all other submission types: the end of the reporting or transition period.  The format of the date is YYYY-MM-DD.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentPeriodEndDate</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:dateItemType</td>
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<td><strong> Balance Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentQuarterlyReport">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true only for a form used as an quarterly report.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-Q<br> -Number 240<br> -Section 308<br> -Subsection a<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentQuarterlyReport</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td>duration</td>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentTransitionReport">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true only for a form used as a transition report.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Forms 10-K, 10-Q, 20-F<br> -Number 240<br> -Section 13<br> -Subsection a-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentTransitionReport</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentType">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The type of document being provided (such as 10-K, 10-Q, 485BPOS, etc). The document type is limited to the same value as the supporting SEC submission type, or the word 'Other'.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentType</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:submissionTypeItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressAddressLine1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Address Line 1 such as Attn, Building Name, Street Name</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressAddressLine1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressCityOrTown">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Name of the City or Town</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressCityOrTown</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressPostalZipCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Code for the postal or zip code</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressPostalZipCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressStateOrProvince">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Name of the state or province.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressStateOrProvince</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:stateOrProvinceItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCentralIndexKey">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A unique 10-digit SEC-issued value to identify entities that have filed disclosures with the SEC. It is commonly abbreviated as CIK.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCentralIndexKey</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:centralIndexKeyItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate number of shares or other units outstanding of each of registrant's classes of capital or common stock or other ownership interests, if and as stated on cover of related periodic report. Where multiple classes or units exist define each class/interest by adding class of stock items such as Common Class A [Member], Common Class B [Member] or Partnership Interest [Member] onto the Instrument [Domain] of the Entity Listings, Instrument.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCommonStockSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCurrentReportingStatus">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate 'Yes' or 'No' whether registrants (1) have filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that registrants were required to file such reports), and (2) have been subject to such filing requirements for the past 90 days. This information should be based on the registrant's current or most recent filing containing the related disclosure.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCurrentReportingStatus</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:yesNoItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityEmergingGrowthCompany">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate if registrant meets the emerging growth company criteria.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityEmergingGrowthCompany</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityFileNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Commission file number. The field allows up to 17 characters. The prefix may contain 1-3 digits, the sequence number may contain 1-8 digits, the optional suffix may contain 1-4 characters, and the fields are separated with a hyphen.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityFileNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:fileNumberItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityFilerCategory">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate whether the registrant is one of the following: Large Accelerated Filer, Accelerated Filer, Non-accelerated Filer. Definitions of these categories are stated in Rule 12b-2 of the Exchange Act. This information should be based on the registrant's current or most recent filing containing the related disclosure.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityFilerCategory</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:filerCategoryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityIncorporationStateCountryCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Two-character EDGAR code representing the state or country of incorporation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityIncorporationStateCountryCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:edgarStateCountryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityInteractiveDataCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-T<br> -Number 232<br> -Section 405<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityInteractiveDataCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:yesNoItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityRegistrantName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The exact name of the entity filing the report as specified in its charter, which is required by forms filed with the SEC.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityRegistrantName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityShellCompany">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the registrant is a shell company as defined in Rule 12b-2 of the Exchange Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityShellCompany</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntitySmallBusiness">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicates that the company is a Smaller Reporting Company (SRC).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntitySmallBusiness</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityTaxIdentificationNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The Tax Identification Number (TIN), also known as an Employer Identification Number (EIN), is a unique 9-digit value assigned by the IRS.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityTaxIdentificationNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:employerIdItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_LocalPhoneNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Local phone number for entity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_LocalPhoneNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_Security12bTitle">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Title of a 12(b) registered security.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_Security12bTitle</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:securityTitleItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_SecurityExchangeName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Name of the Exchange on which a security is registered.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection d1-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_SecurityExchangeName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:edgarExchangeCodeItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_TradingSymbol">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Trading symbol of an instrument as listed on an exchange.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_TradingSymbol</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:tradingSymbolItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>12
<FILENAME>R2.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592581807104">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED BALANCE SHEETS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsCurrentAbstract', window );"><strong>Current assets:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents</a></td>
<td class="nump">$ 314,993<span></span>
</td>
<td class="nump">$ 869,191<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShortTermInvestments', window );">Short-term investments</a></td>
<td class="nump">1,666,670<span></span>
</td>
<td class="nump">1,245,782<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetNetCurrent', window );">Contracts receivable</a></td>
<td class="nump">6,645<span></span>
</td>
<td class="nump">61,896<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryNet', window );">Inventories</a></td>
<td class="nump">20,645<span></span>
</td>
<td class="nump">24,806<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherAssetsCurrent', window );">Other current assets</a></td>
<td class="nump">143,173<span></span>
</td>
<td class="nump">143,374<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsCurrent', window );">Total current assets</a></td>
<td class="nump">2,152,126<span></span>
</td>
<td class="nump">2,345,049<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="nump">180,806<span></span>
</td>
<td class="nump">178,069<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsNet', window );">Patents, net</a></td>
<td class="nump">29,605<span></span>
</td>
<td class="nump">29,005<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherAssetsNoncurrent', window );">Deposits and other assets</a></td>
<td class="nump">59,434<span></span>
</td>
<td class="nump">59,567<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets</a></td>
<td class="nump">2,421,971<span></span>
</td>
<td class="nump">2,611,690<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrentAbstract', window );"><strong>Current liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccountsPayableCurrent', window );">Accounts payable</a></td>
<td class="nump">20,545<span></span>
</td>
<td class="nump">11,904<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeRelatedLiabilitiesCurrent', window );">Accrued compensation</a></td>
<td class="nump">30,410<span></span>
</td>
<td class="nump">38,810<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrent', window );">Accrued liabilities</a></td>
<td class="nump">128,002<span></span>
</td>
<td class="nump">88,560<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccruedIncomeTaxesCurrent', window );">Income taxes payable</a></td>
<td class="nump">16<span></span>
</td>
<td class="nump">36<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LongTermObligationsExcludingConvertibleDebtCurrent', window );">Current portion of long-term obligations</a></td>
<td class="nump">4,970<span></span>
</td>
<td class="nump">3,526<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred contract revenue</a></td>
<td class="nump">99,511<span></span>
</td>
<td class="nump">97,714<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrent', window );">Total current liabilities</a></td>
<td class="nump">283,454<span></span>
</td>
<td class="nump">240,550<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityNoncurrent', window );">Long-term deferred contract revenue</a></td>
<td class="nump">294,656<span></span>
</td>
<td class="nump">351,879<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LongTermObligationsExcludingConvertibleDebtNoncurrent', window );">Long-term obligations, less current portion</a></td>
<td class="nump">25,107<span></span>
</td>
<td class="nump">26,378<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermLoansFromBank', window );">Long-term mortgage debt</a></td>
<td class="nump">58,978<span></span>
</td>
<td class="nump">59,713<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Liabilities', window );">Total liabilities</a></td>
<td class="nump">1,827,610<span></span>
</td>
<td class="nump">1,839,953<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityAbstract', window );"><strong>Stockholders' equity:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockValue', window );">Common stock, $0.001 par value; 300,000,000 shares authorized, 142,017,411 and 141,210,015 shares issued and outstanding at September 30, 2022 (unaudited) and December 31, 2021, respectively</a></td>
<td class="nump">142<span></span>
</td>
<td class="nump">141<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdditionalPaidInCapitalCommonStock', window );">Additional paid-in capital</a></td>
<td class="nump">2,034,554<span></span>
</td>
<td class="nump">1,964,167<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax', window );">Accumulated other comprehensive loss</a></td>
<td class="num">(63,140)<span></span>
</td>
<td class="num">(32,668)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RetainedEarningsAccumulatedDeficit', window );">Accumulated deficit</a></td>
<td class="num">(1,377,195)<span></span>
</td>
<td class="num">(1,159,903)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquity', window );">Total stockholders' equity</a></td>
<td class="nump">594,361<span></span>
</td>
<td class="nump">771,737<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquity', window );">Total liabilities and stockholders' equity</a></td>
<td class="nump">2,421,971<span></span>
</td>
<td class="nump">2,611,690<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrentAbstract', window );"><strong>Current liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtNoncurrent', window );">Convertible senior notes, net</a></td>
<td class="nump">621,460<span></span>
</td>
<td class="nump">619,119<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrentAbstract', window );"><strong>Current liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtNoncurrent', window );">Convertible senior notes, net</a></td>
<td class="nump">$ 543,955<span></span>
</td>
<td class="nump">$ 542,314<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LongTermObligationsExcludingConvertibleDebtCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt and lease obligations, excluding convertible debt, classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LongTermObligationsExcludingConvertibleDebtCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LongTermObligationsExcludingConvertibleDebtNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt and lease obligations, excluding convertible debt, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LongTermObligationsExcludingConvertibleDebtNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccountsPayableCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of liabilities incurred (and for which invoices have typically been received) and payable to vendors for goods and services received that are used in an entity's business. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccountsPayableCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedIncomeTaxesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying amount as of the balance sheet date of the unpaid sum of the known and estimated amounts payable to satisfy all currently due domestic and foreign income tax obligations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(15)(b)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(15)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedIncomeTaxesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred and payable, pertaining to costs that are statutory in nature, are incurred on contractual obligations, or accumulate over time and for which invoices have not yet been received or will not be rendered. Examples include taxes, interest, rent and utilities. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Accumulated change in equity from transactions and other events and circumstances from non-owner sources, net of tax effect, at period end. Excludes Net Income (Loss), and accumulated changes in equity from transactions resulting from investments by owners and distributions to owners. Includes foreign currency translation items, certain pension adjustments, unrealized gains and losses on certain investments in debt and equity securities, other than temporary impairment (OTTI) losses related to factors other than credit losses on available-for-sale and held-to-maturity debt securities that an entity does not intend to sell and it is not more likely than not that the entity will be required to sell before recovery of the amortized cost basis, as well as changes in the fair value of derivatives related to the effective portion of a designated cash flow hedge.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(4))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=d3e637-108580<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(3))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14A<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669686-108580<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (h)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=124501264&amp;loc=SL117420844-207641<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=124501264&amp;loc=SL117420844-207641<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=d3e681-108580<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdditionalPaidInCapitalCommonStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Value received from shareholders in common stock-related transactions that are in excess of par value or stated value and amounts received from other stock-related transactions. Includes only common stock transactions (excludes preferred stock transactions). May be called contributed capital, capital in excess of par, capital surplus, or paid-in capital.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdditionalPaidInCapitalCommonStock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Assets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Sum of the carrying amounts as of the balance sheet date of all assets that are recognized. Assets are probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(11))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(A))<br> -URI 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-Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 20: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=116870748&amp;loc=SL6758485-165988<br><br>Reference 21: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442552-122756<br><br>Reference 22: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(18))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 23: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 24: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_Assets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AssetsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Sum of the carrying amounts as of the balance sheet date of all assets that are expected to be realized in cash, sold, or consumed within one year (or the normal operating cycle, if longer). Assets are probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124098289&amp;loc=d3e6676-107765<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124433192&amp;loc=SL2890621-112765<br><br>Reference 4: 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FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442552-122756<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=116870748&amp;loc=SL6758485-165988<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(B))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442552-122756<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 14: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(ii))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442526-122756<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442552-122756<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (bb)<br> -URI https://asc.fasb.org/extlink&amp;oid=123419778&amp;loc=d3e5710-111685<br><br>Reference 17: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iv))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442526-122756<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(9))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 19: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AssetsCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetsCurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashAndCashEquivalentsAtCarryingValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of currency on hand as well as demand deposits with banks or financial institutions. Includes other kinds of accounts that have the general characteristics of demand deposits. Also includes short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates. Excludes cash and cash equivalents within disposal group and discontinued operation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3044-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124098289&amp;loc=d3e6676-107765<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashAndCashEquivalentsAtCarryingValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Aggregate par or stated value of issued nonredeemable common stock (or common stock redeemable solely at the option of the issuer). This item includes treasury stock repurchased by the entity. Note: elements for number of nonredeemable common shares, par value and other disclosure concepts are in another section within stockholders' equity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerAssetNetCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after allowance for credit loss, of right to consideration in exchange for good or service transferred to customer when right is conditioned on something other than passage of time, classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130533-203044<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerAssetNetCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiabilityCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable, classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130532-203044<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiabilityNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130532-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConvertibleDebtNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying amount of long-term convertible debt as of the balance sheet date, net of the amount due in the next twelve months or greater than the normal operating cycle, if longer. The debt is convertible into another form of financial instrument, typically the entity's common stock.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConvertibleDebtNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeRelatedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of the carrying values as of the balance sheet date of obligations incurred through that date and payable for obligations related to services received from employees, such as accrued salaries and bonuses, payroll taxes and fringe benefits. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeRelatedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FiniteLivedIntangibleAssetsNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after amortization of assets, excluding financial assets and goodwill, lacking physical substance with a finite life.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 926<br> -SubTopic 20<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=120154696&amp;loc=d3e54445-107959<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FiniteLivedIntangibleAssetsNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after valuation and LIFO reserves of inventory expected to be sold, or consumed within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124098289&amp;loc=d3e6676-107765<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Liabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Sum of the carrying amounts as of the balance sheet date of all liabilities that are recognized. Liabilities are probable future sacrifices of economic benefits arising from present obligations of an entity to transfer assets or provide services to other entities in the future.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19-26)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124433192&amp;loc=SL2890621-112765<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (d)<br> -URI 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_Liabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesAndStockholdersEquity">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of liabilities and equity items, including the portion of equity attributable to noncontrolling interests, if any.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(23))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(25))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(32))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 7: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=123596393&amp;loc=d3e14064-108612<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesAndStockholdersEquity</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total obligations incurred as part of normal operations that are expected to be paid during the following twelve months or within one business cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124433192&amp;loc=SL2890621-112765<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(A))<br> -URI 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesCurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermLoansFromBank">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of loans from a bank with maturities initially due after one year or beyond the operating cycle if longer, excluding current portion.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16)(a)(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermLoansFromBank</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherAssetsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherAssetsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherAssetsNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of noncurrent assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(17))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherAssetsNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after accumulated depreciation, depletion and amortization of physical assets used in the normal conduct of business to produce goods and services and not intended for resale. Examples include, but are not limited to, land, buildings, machinery and equipment, office equipment, and furniture and fixtures.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 360<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124429447&amp;loc=SL124453093-239630<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RetainedEarningsAccumulatedDeficit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cumulative amount of the reporting entity's undistributed earnings or deficit.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(3))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(4))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (h)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=124501264&amp;loc=SL117420844-207641<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI https://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=124501264&amp;loc=SL117420844-207641<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RetainedEarningsAccumulatedDeficit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShortTermInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investments including trading securities, available-for-sale securities, held-to-maturity securities, and short-term investments classified as other and current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(4))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(5))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(1)(g))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShortTermInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockholdersEquity">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of all stockholders' equity (deficit) items, net of receivables from officers, directors, owners, and affiliates of the entity which are attributable to the parent. The amount of the economic entity's stockholders' equity attributable to the parent excludes the amount of stockholders' equity which is allocable to that ownership interest in subsidiary equity which is not attributable to the parent (noncontrolling interest, minority interest). This excludes temporary equity and is sometimes called permanent equity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 4.E)<br> -URI https://asc.fasb.org/extlink&amp;oid=122038336&amp;loc=d3e74512-122707<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(31))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 7: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=123596393&amp;loc=d3e14064-108612<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquity</td>
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<td><strong> Balance Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
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<tr>
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<td><strong> Period Type:</strong></td>
<td></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
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<tr>
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<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td></td>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592581617728">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares<br></strong></div></th>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityAbstract', window );"><strong>Stockholders' equity:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockParOrStatedValuePerShare', window );">Common stock, par value (in dollars per share)</a></td>
<td class="nump">$ 0.001<span></span>
</td>
<td class="nump">$ 0.001<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesAuthorized', window );">Common stock, shares authorized (in shares)</a></td>
<td class="nump">300,000,000<span></span>
</td>
<td class="nump">300,000,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="nump">142,017,411<span></span>
</td>
<td class="nump">141,210,015<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesOutstanding', window );">Common stock, shares outstanding (in shares)</a></td>
<td class="nump">142,017,411<span></span>
</td>
<td class="nump">141,210,015<span></span>
</td>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
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<td class="nump">0.125%<span></span>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockParOrStatedValuePerShare">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face amount or stated value per share of common stock.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockParOrStatedValuePerShare</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>dtr-types:perShareItemType</td>
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<td>na</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum number of common shares permitted to be issued by an entity's charter and bylaws.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesAuthorized</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>na</td>
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<td>instant</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total number of common shares of an entity that have been sold or granted to shareholders (includes common shares that were issued, repurchased and remain in the treasury). These shares represent capital invested by the firm's shareholders and owners, and may be all or only a portion of the number of shares authorized. Shares issued include shares outstanding and shares held in the treasury.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares of common stock outstanding. Common stock represent the ownership interest in a corporation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesAndStockholdersEquityAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592580813152">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 159,767<span></span>
</td>
<td class="nump">$ 133,093<span></span>
</td>
<td class="nump">$ 435,478<span></span>
</td>
<td class="nump">$ 370,450<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostsAndExpensesAbstract', window );"><strong>Expenses:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostOfGoodsAndServicesSold', window );">Cost of sales</a></td>
<td class="nump">1,515<span></span>
</td>
<td class="nump">3,079<span></span>
</td>
<td class="nump">10,430<span></span>
</td>
<td class="nump">8,616<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ResearchDevelopmentAndPatentExpense', window );">Research, development and patent</a></td>
<td class="nump">182,990<span></span>
</td>
<td class="nump">184,770<span></span>
</td>
<td class="nump">524,875<span></span>
</td>
<td class="nump">463,878<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SellingGeneralAndAdministrativeExpense', window );">Selling, general and administrative</a></td>
<td class="nump">34,416<span></span>
</td>
<td class="nump">31,093<span></span>
</td>
<td class="nump">102,345<span></span>
</td>
<td class="nump">148,747<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">218,921<span></span>
</td>
<td class="nump">218,942<span></span>
</td>
<td class="nump">637,650<span></span>
</td>
<td class="nump">621,241<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Loss from operations</a></td>
<td class="num">(59,154)<span></span>
</td>
<td class="num">(85,849)<span></span>
</td>
<td class="num">(202,172)<span></span>
</td>
<td class="num">(250,791)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NonoperatingIncomeExpenseAbstract', window );"><strong>Other income (expense):</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentIncomeNet', window );">Investment income, net</a></td>
<td class="nump">7,524<span></span>
</td>
<td class="nump">872<span></span>
</td>
<td class="nump">13,447<span></span>
</td>
<td class="nump">8,236<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InterestExpense', window );">Interest expense</a></td>
<td class="num">(2,139)<span></span>
</td>
<td class="num">(2,340)<span></span>
</td>
<td class="num">(6,391)<span></span>
</td>
<td class="num">(7,111)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainLossOnInvestments', window );">Gain (loss) on investments</a></td>
<td class="nump">2,347<span></span>
</td>
<td class="nump">4,013<span></span>
</td>
<td class="num">(10,616)<span></span>
</td>
<td class="nump">4,885<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherNonoperatingIncomeExpense', window );">Other income (expense)</a></td>
<td class="nump">4,713<span></span>
</td>
<td class="num">(469)<span></span>
</td>
<td class="num">(7,923)<span></span>
</td>
<td class="num">(9,283)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest', window );">Loss before income tax (expense) benefit</a></td>
<td class="num">(46,709)<span></span>
</td>
<td class="num">(83,773)<span></span>
</td>
<td class="num">(213,655)<span></span>
</td>
<td class="num">(254,064)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Income tax (expense) benefit</a></td>
<td class="num">(283)<span></span>
</td>
<td class="nump">1,307<span></span>
</td>
<td class="num">(3,637)<span></span>
</td>
<td class="nump">854<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (46,992)<span></span>
</td>
<td class="num">$ (82,466)<span></span>
</td>
<td class="num">$ (217,292)<span></span>
</td>
<td class="num">$ (253,210)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net loss per share (in dollars per share)</a></td>
<td class="num">$ (0.33)<span></span>
</td>
<td class="num">$ (0.58)<span></span>
</td>
<td class="num">$ (1.53)<span></span>
</td>
<td class="num">$ (1.8)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareDiluted', window );">Diluted net loss per share (in dollars per share)</a></td>
<td class="num">$ (0.33)<span></span>
</td>
<td class="num">$ (0.58)<span></span>
</td>
<td class="num">$ (1.53)<span></span>
</td>
<td class="num">$ (1.8)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic', window );">Shares used in computing basic net loss per share (in shares)</a></td>
<td class="nump">141,950<span></span>
</td>
<td class="nump">141,139<span></span>
</td>
<td class="nump">141,782<span></span>
</td>
<td class="nump">140,958<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net loss per share (in shares)</a></td>
<td class="nump">141,950<span></span>
</td>
<td class="nump">141,139<span></span>
</td>
<td class="nump">141,782<span></span>
</td>
<td class="nump">140,958<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_CommercialMember', window );">Commercial Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 72,410<span></span>
</td>
<td class="nump">$ 84,820<span></span>
</td>
<td class="nump">$ 222,879<span></span>
</td>
<td class="nump">$ 255,129<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember', window );">SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">61,647<span></span>
</td>
<td class="nump">66,572<span></span>
</td>
<td class="nump">175,092<span></span>
</td>
<td class="nump">198,726<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=us-gaap_ProductMember', window );">TEGSEDI and WAYLIVRA Revenue, Net [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">5,920<span></span>
</td>
<td class="nump">15,519<span></span>
</td>
<td class="nump">22,467<span></span>
</td>
<td class="nump">46,901<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember', window );">Licensing and Other Royalty Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">4,843<span></span>
</td>
<td class="nump">2,729<span></span>
</td>
<td class="nump">25,320<span></span>
</td>
<td class="nump">9,502<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember', window );">Research and Development Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">87,357<span></span>
</td>
<td class="nump">48,273<span></span>
</td>
<td class="nump">212,599<span></span>
</td>
<td class="nump">115,321<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_CollaborativeAgreementRevenueMember', window );">Collaborative Agreement Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">69,250<span></span>
</td>
<td class="nump">48,273<span></span>
</td>
<td class="nump">157,282<span></span>
</td>
<td class="nump">115,321<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_EplontersenJointDevelopmentRevenueMember', window );">Eplontersen Joint Development Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 18,107<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 55,317<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ResearchDevelopmentAndPatentExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate costs incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process whether intended for sale or the entity's use, during the reporting period charged to research and development projects. Also includes charges for amortization and write-downs of capitalized patent costs, as well as legal fees for patent litigation and patent defense.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ResearchDevelopmentAndPatentExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostOfGoodsAndServicesSold">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate costs related to goods produced and sold and services rendered by an entity during the reporting period. This excludes costs incurred during the reporting period related to financial services rendered and other revenue generating activities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI https://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.2(a),(d))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostOfGoodsAndServicesSold</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostsAndExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total costs of sales and operating expenses for the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostsAndExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
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<tr>
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<td>duration</td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostsAndExpensesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostsAndExpensesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(4)<br> -URI https://asc.fasb.org/extlink&amp;oid=126732423&amp;loc=SL123482106-238011<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22583-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 4: 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareDiluted">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period available to each share of common stock or common unit outstanding during the reporting period and to each share or unit that would have been outstanding assuming the issuance of common shares or units for all dilutive potential common shares or units outstanding during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 52<br> -URI https://asc.fasb.org/extlink&amp;oid=128363288&amp;loc=d3e4984-109258<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22644-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 15<br> -URI https://asc.fasb.org/extlink&amp;oid=128363288&amp;loc=d3e3842-109258<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1252-109256<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22595-107794<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22583-107794<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=SL5780133-109256<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126732423&amp;loc=SL123482106-238011<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1337-109256<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(4)<br> -URI https://asc.fasb.org/extlink&amp;oid=126732423&amp;loc=SL123482106-238011<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(25))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareDiluted</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainLossOnInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of realized and unrealized gain (loss) on investment.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27405-111563<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.7(c),9(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 3: http://www.xbrl.org/2003/role/recommendedDisclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainLossOnInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of income (loss) from continuing operations, including income (loss) from equity method investments, before deduction of income tax expense (benefit), and income (loss) attributable to noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 940<br> -SubTopic 20<br> -Section 25<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126941158&amp;loc=d3e41242-110953<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(10))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 235<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-05(b)(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399901&amp;loc=d3e537907-122884<br><br>Reference 9: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8924-108599<br><br>Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(15))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.7)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32672-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22663-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123586238&amp;loc=d3e38679-109324<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22658-107794<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InterestExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the cost of borrowed funds accounted for as interest expense.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=6450988&amp;loc=d3e26243-108391<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28555-108399<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (210.5-03(11))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04.9)<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InterestExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentIncomeNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after accretion (amortization) of discount (premium), and investment expense, of interest income and dividend income on nonoperating securities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.7(a),(b))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.8)<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentIncomeNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NonoperatingIncomeExpenseAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NonoperatingIncomeExpenseAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The net result for the period of deducting operating expenses from operating revenues.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8924-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherNonoperatingIncomeExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of income (expense) related to nonoperating activities, classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.9)<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherNonoperatingIncomeExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI https://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenuesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenuesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SellingGeneralAndAdministrativeExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate total costs related to selling a firm's product and services, as well as all other general and administrative expenses. Direct selling expenses (for example, credit, warranty, and advertising) are expenses that can be directly linked to the sale of specific products. Indirect selling expenses are expenses that cannot be directly linked to the sale of specific products, for example telephone expenses, Internet, and postal charges. General and administrative expenses include salaries of non-sales personnel, rent, utilities, communication, etc.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.4)<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SellingGeneralAndAdministrativeExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The average number of shares or units issued and outstanding that are used in calculating diluted EPS or earnings per unit (EPU), determined based on the timing of issuance of shares or units in the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1505-109256<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of [basic] shares or units, after adjustment for contingently issuable shares or units and other shares or units not deemed outstanding, determined by relating the portion of time within a reporting period that common shares or units have been outstanding to the total time in that period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1448-109256<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberOfSharesOutstandingBasic</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_CommercialMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_CommercialMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=us-gaap_ProductMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
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<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_CollaborativeAgreementRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_CollaborativeAgreementRevenueMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_EplontersenJointDevelopmentRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_EplontersenJointDevelopmentRevenueMember</td>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592581859664">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract', window );"><strong>CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (46,992)<span></span>
</td>
<td class="num">$ (82,466)<span></span>
</td>
<td class="num">$ (217,292)<span></span>
</td>
<td class="num">$ (253,210)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax', window );">Unrealized losses on debt securities, net of tax</a></td>
<td class="num">(8,734)<span></span>
</td>
<td class="num">(1,618)<span></span>
</td>
<td class="num">(29,508)<span></span>
</td>
<td class="num">(6,321)<span></span>
</td>
</tr>
<tr class="ro">
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<td class="num">(399)<span></span>
</td>
<td class="num">(23)<span></span>
</td>
<td class="num">(964)<span></span>
</td>
<td class="num">(45)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTax', window );">Comprehensive loss</a></td>
<td class="num">$ (56,125)<span></span>
</td>
<td class="num">$ (84,107)<span></span>
</td>
<td class="num">$ (247,764)<span></span>
</td>
<td class="num">$ (259,576)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ComprehensiveIncomeNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax of increase (decrease) in equity from transactions and other events and circumstances from net income and other comprehensive income, attributable to parent entity. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(24))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=d3e557-108580<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(26))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669625-108580<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669619-108580<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ComprehensiveIncomeNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax, before reclassification adjustments of gain (loss) on foreign currency translation adjustments, foreign currency transactions designated and effective as economic hedges of a net investment in a foreign entity and intra-entity foreign currency transactions that are of a long-term-investment nature.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 20<br> -Section 35<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=123602790&amp;loc=d3e30304-110892<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 10<br> -Section 45<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=126980362&amp;loc=d3e28129-110885<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32022-110900<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (a-c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669646-108580<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after tax and before adjustment, of unrealized holding gain (loss) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale). Excludes unrealized gain (loss) on investment in debt security measured at amortized cost (held-to-maturity) from transfer to available-for-sale.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669646-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract">
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<td style="white-space:nowrap;">us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:stringItemType</td>
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<td>na</td>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>16
<FILENAME>R6.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592580040768">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th"><div>Common Stock [Member]</div></th>
<th class="th"><div>Additional Paid In Capital [Member]</div></th>
<th class="th"><div>Accumulated Other Comprehensive Loss [Member]</div></th>
<th class="th"><div>Accumulated Deficit [Member]</div></th>
<th class="th"><div>Total</div></th>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2020</a></td>
<td class="nump">$ 140<span></span>
</td>
<td class="nump">$ 1,895,519<span></span>
</td>
<td class="num">$ (21,071)<span></span>
</td>
<td class="num">$ (1,131,306)<span></span>
</td>
<td class="nump">$ 743,282<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2020</a></td>
<td class="nump">140,366<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(253,210)<span></span>
</td>
<td class="num">(253,210)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized losses, net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(6,321)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(6,321)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(45)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(45)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 1<span></span>
</td>
<td class="nump">11,563<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">11,564<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">1,094<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued', window );">Issuance of warrants</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">89,752<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">89,752<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalOther', window );">Purchase of note hedges</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(136,620)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(136,620)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">98,419<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">98,419<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(16,285)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(16,285)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)</a></td>
<td class="num">(276)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Sep. 30, 2021</a></td>
<td class="nump">$ 141<span></span>
</td>
<td class="nump">1,942,348<span></span>
</td>
<td class="num">(27,437)<span></span>
</td>
<td class="num">(1,384,516)<span></span>
</td>
<td class="nump">530,536<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Sep. 30, 2021</a></td>
<td class="nump">141,184<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Jun. 30, 2021</a></td>
<td class="nump">$ 141<span></span>
</td>
<td class="nump">1,910,379<span></span>
</td>
<td class="num">(25,796)<span></span>
</td>
<td class="num">(1,302,050)<span></span>
</td>
<td class="nump">582,674<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Jun. 30, 2021</a></td>
<td class="nump">141,022<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(82,466)<span></span>
</td>
<td class="num">(82,466)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized losses, net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(1,618)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(1,618)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(23)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(23)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">1,922<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">1,922<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">176<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued', window );">Issuance of warrants</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalOther', window );">Purchase of note hedges</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">30,537<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">30,537<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(490)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(490)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)</a></td>
<td class="num">(14)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Sep. 30, 2021</a></td>
<td class="nump">$ 141<span></span>
</td>
<td class="nump">1,942,348<span></span>
</td>
<td class="num">(27,437)<span></span>
</td>
<td class="num">(1,384,516)<span></span>
</td>
<td class="nump">530,536<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Sep. 30, 2021</a></td>
<td class="nump">141,184<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2021</a></td>
<td class="nump">$ 141<span></span>
</td>
<td class="nump">1,964,167<span></span>
</td>
<td class="num">(32,668)<span></span>
</td>
<td class="num">(1,159,903)<span></span>
</td>
<td class="nump">771,737<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2021</a></td>
<td class="nump">141,210<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(217,292)<span></span>
</td>
<td class="num">(217,292)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized losses, net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(29,508)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(29,508)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(964)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(964)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 1<span></span>
</td>
<td class="nump">6,029<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,030<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">1,138<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">74,575<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">74,575<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(10,217)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,217)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)</a></td>
<td class="num">(331)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Sep. 30, 2022</a></td>
<td class="nump">$ 142<span></span>
</td>
<td class="nump">2,034,554<span></span>
</td>
<td class="num">(63,140)<span></span>
</td>
<td class="num">(1,377,195)<span></span>
</td>
<td class="nump">594,361<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Sep. 30, 2022</a></td>
<td class="nump">142,017<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Jun. 30, 2022</a></td>
<td class="nump">$ 142<span></span>
</td>
<td class="nump">2,008,794<span></span>
</td>
<td class="num">(54,007)<span></span>
</td>
<td class="num">(1,330,203)<span></span>
</td>
<td class="nump">624,726<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Jun. 30, 2022</a></td>
<td class="nump">141,831<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(46,992)<span></span>
</td>
<td class="num">(46,992)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized losses, net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(8,734)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(8,734)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(399)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(399)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">2,567<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">2,567<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">203<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">23,837<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">23,837<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(644)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(644)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)</a></td>
<td class="num">(17)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Sep. 30, 2022</a></td>
<td class="nump">$ 142<span></span>
</td>
<td class="nump">$ 2,034,554<span></span>
</td>
<td class="num">$ (63,140)<span></span>
</td>
<td class="num">$ (1,377,195)<span></span>
</td>
<td class="nump">$ 594,361<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Sep. 30, 2022</a></td>
<td class="nump">142,017<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of decrease to equity for grantee's tax withholding obligation for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of other increase (decrease) in additional paid in capital (APIC).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToAdditionalPaidInCapitalOther</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase to additional paid-in capital (APIC) for recognition of cost for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=126964447&amp;loc=d3e11149-113907<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 13<br> -URI https://asc.fasb.org/extlink&amp;oid=126964447&amp;loc=d3e11178-113907<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 35<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126961718&amp;loc=d3e4534-113899<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase in additional paid in capital (APIC) resulting from the issuance of warrants. Includes allocation of proceeds of debt securities issued with detachable stock purchase warrants.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 25<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=123466302&amp;loc=d3e4724-112606<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI https://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInStockholdersEquityRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax and reclassification adjustments, of appreciation (loss) in value of unsold available-for-sale securities, attributable to parent entity. Excludes amounts related to other than temporary impairment (OTTI) loss.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI https://asc.fasb.org/extlink&amp;oid=126929396&amp;loc=SL4569616-111683<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=126929396&amp;loc=SL4569643-111683<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax, before reclassification adjustments of gain (loss) on foreign currency translation adjustments, foreign currency transactions designated and effective as economic hedges of a net investment in a foreign entity and intra-entity foreign currency transactions that are of a long-term-investment nature.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 20<br> -Section 35<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=123602790&amp;loc=d3e30304-110892<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 10<br> -Section 45<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=126980362&amp;loc=d3e28129-110885<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32022-110900<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (a-c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669646-108580<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares of stock issued as of the balance sheet date, including shares that had been issued and were previously outstanding but which are now held in the treasury.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares used to settle grantee's tax withholding obligation for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number, after forfeiture, of shares or units issued under share-based payment arrangement. Excludes shares or units issued under employee stock ownership plan (ESOP).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI https://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Value, before forfeiture, of shares issued under share-based payment arrangement. Excludes employee stock ownership plan (ESOP).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of stockholders' equity (deficit), net of receivables from officers, directors, owners, and affiliates of the entity, attributable to both the parent and noncontrolling interests. Amount excludes temporary equity. Alternate caption for the concept is permanent equity.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592581737408">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Operating activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (217,292)<span></span>
</td>
<td class="num">$ (253,210)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Adjustments to reconcile net loss to net cash used in operating activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Depreciation', window );">Depreciation</a></td>
<td class="nump">11,301<span></span>
</td>
<td class="nump">11,665<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense', window );">Amortization of right-of-use operating lease assets</a></td>
<td class="nump">1,970<span></span>
</td>
<td class="nump">1,171<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AmortizationOfIntangibleAssets', window );">Amortization of patents</a></td>
<td class="nump">1,805<span></span>
</td>
<td class="nump">1,740<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments', window );">Amortization of premium on investments, net</a></td>
<td class="nump">9,072<span></span>
</td>
<td class="nump">13,515<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="nump">4,035<span></span>
</td>
<td class="nump">3,586<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensation', window );">Stock-based compensation expense</a></td>
<td class="nump">74,575<span></span>
</td>
<td class="nump">98,419<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RealizedInvestmentGainsLosses', window );">Loss (gain) on investments</a></td>
<td class="nump">228<span></span>
</td>
<td class="num">(933)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Loss on early retirement of debt</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">8,627<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainLossOnDispositionOfAssets', window );">Non-cash losses related to disposal of property, plant and equipment</a></td>
<td class="nump">528<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ImpairmentOfIntangibleAssetsFinitelived', window );">Non-cash losses related to patents</a></td>
<td class="nump">1,155<span></span>
</td>
<td class="nump">1,150<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOperatingCapitalAbstract', window );"><strong>Changes in operating assets and liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInContractWithCustomerAsset', window );">Contracts receivable</a></td>
<td class="nump">55,251<span></span>
</td>
<td class="nump">67,136<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInInventories', window );">Inventories</a></td>
<td class="nump">4,161<span></span>
</td>
<td class="num">(965)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherOperatingAssets', window );">Other current and long-term assets</a></td>
<td class="num">(988)<span></span>
</td>
<td class="nump">10,358<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable', window );">Income taxes payable</a></td>
<td class="num">(20)<span></span>
</td>
<td class="nump">134<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInAccountsPayable', window );">Accounts payable</a></td>
<td class="nump">5,607<span></span>
</td>
<td class="num">(10,737)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities', window );">Accrued compensation</a></td>
<td class="num">(8,400)<span></span>
</td>
<td class="num">(33,408)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherCurrentLiabilities', window );">Accrued liabilities and other current liabilities</a></td>
<td class="nump">38,263<span></span>
</td>
<td class="num">(19,526)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="num">(55,426)<span></span>
</td>
<td class="num">(71,610)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInOperatingActivities', window );">Net cash used in operating activities</a></td>
<td class="num">(74,175)<span></span>
</td>
<td class="num">(172,888)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract', window );"><strong>Investing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt', window );">Purchases of short-term investments</a></td>
<td class="num">(1,223,791)<span></span>
</td>
<td class="num">(930,963)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities', window );">Proceeds from sale of short-term investments</a></td>
<td class="nump">764,101<span></span>
</td>
<td class="nump">1,051,857<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment', window );">Purchases of property, plant and equipment</a></td>
<td class="num">(11,582)<span></span>
</td>
<td class="num">(9,453)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireIntangibleAssets', window );">Acquisition of licenses and other assets, net</a></td>
<td class="num">(3,511)<span></span>
</td>
<td class="num">(4,459)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireEquitySecuritiesFvNi', window );">Purchase of Bicycle Therapeutics plc common stock</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(7,185)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInInvestingActivities', window );">Net cash (used in) provided by investing activities</a></td>
<td class="num">(474,783)<span></span>
</td>
<td class="nump">99,797<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract', window );"><strong>Financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions', window );">Proceeds from equity, net</a></td>
<td class="nump">6,030<span></span>
</td>
<td class="nump">11,564<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="num">(10,217)<span></span>
</td>
<td class="num">(16,285)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromConvertibleDebt', window );">Proceeds from the issuance of 0 percent convertible notes</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">632,500<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsOfDebtIssuanceCosts', window );">0 percent convertible senior notes issuance costs</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(15,525)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfConvertibleDebt', window );">Repurchase of $247.9 million principal amount of the 1 percent convertible senior notes</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(256,963)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfWarrants', window );">Proceeds from issuance of warrants</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">89,752<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(136,620)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfSecuredDebt', window );">Principal payments on mortgage debt</a></td>
<td class="num">(89)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivities', window );">Net cash (used in) provided by financing activities</a></td>
<td class="num">(4,276)<span></span>
</td>
<td class="nump">308,423<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations', window );">Effects of exchange rates on cash</a></td>
<td class="num">(964)<span></span>
</td>
<td class="num">(43)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect', window );">Net (decrease) increase in cash and cash equivalents</a></td>
<td class="num">(554,198)<span></span>
</td>
<td class="nump">235,289<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at beginning of period</a></td>
<td class="nump">869,191<span></span>
</td>
<td class="nump">397,664<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at end of period</a></td>
<td class="nump">314,993<span></span>
</td>
<td class="nump">632,953<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SupplementalCashFlowInformationAbstract', window );"><strong>Supplemental disclosures of cash flow information:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InterestPaidNet', window );">Interest paid</a></td>
<td class="nump">2,204<span></span>
</td>
<td class="nump">3,527<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxesPaid', window );">Income taxes paid</a></td>
<td class="nump">2<span></span>
</td>
<td class="nump">3<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract', window );"><strong>Supplemental disclosures of non-cash investing and financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NonCashCapitalAndPatentExpenditures', window );">Amounts accrued for capital and patent expenditures</a></td>
<td class="nump">3,032<span></span>
</td>
<td class="nump">1,811<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability', window );">Right-of-use assets obtained in exchange for lease liabilities</a></td>
<td class="nump">$ 657<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NonCashCapitalAndPatentExpenditures">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Future cash outflow to pay for purchases of fixed assets and patents that have been incurred.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NonCashCapitalAndPatentExpenditures</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The sum of the periodic adjustments of the differences between securities' face values and purchase prices that are charged against earnings. This is called accretion if the security was purchased at a discount and amortization if it was purchased at premium. As a noncash item, this element is an adjustment to net income when calculating cash provided by or used in operations using the indirect method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AmortizationOfFinancingCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization expense attributable to debt issuance costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1F<br> -Subparagraph (b)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495355-112611<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28555-108399<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AmortizationOfFinancingCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AmortizationOfIntangibleAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate expense charged against earnings to allocate the cost of intangible assets (nonphysical assets not used in production) in a systematic and rational manner to the periods expected to benefit from such assets. As a noncash expense, this element is added back to net income when calculating cash provided by or used in operations using the indirect method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=6388964&amp;loc=d3e16225-109274<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AmortizationOfIntangibleAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash and cash equivalents, and cash and cash equivalents restricted to withdrawal or usage. Excludes amount for disposal group and discontinued operations. Cash includes, but is not limited to, currency on hand, demand deposits with banks or financial institutions, and other accounts with general characteristics of demand deposits. Cash equivalents include, but are not limited to, short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3521-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3044-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=126999549&amp;loc=SL98516268-108586<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in cash, cash equivalents, and cash and cash equivalents restricted to withdrawal or usage; including effect from exchange rate change. Cash includes, but is not limited to, currency on hand, demand deposits with banks or financial institutions, and other accounts with general characteristics of demand deposits. Cash equivalents include, but are not limited to, short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 230<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123444420&amp;loc=d3e33268-110906<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3521-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Depreciation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of expense recognized in the current period that reflects the allocation of the cost of tangible assets over the assets' useful lives. Includes production and non-production related depreciation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_Depreciation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) from effect of exchange rate changes on cash and cash equivalents, and cash and cash equivalents restricted to withdrawal or usage; held in foreign currencies; including, but not limited to, disposal group and discontinued operations. Cash includes, but is not limited to, currency on hand, demand deposits with banks or financial institutions, and other accounts with general characteristics of demand deposits. Cash equivalents include, but are not limited to, short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 230<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123444420&amp;loc=d3e33268-110906<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainLossOnDispositionOfAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of gain (loss) on sale or disposal of property, plant and equipment assets, excluding oil and gas property and timber property.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 45<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126905981&amp;loc=d3e2443-110228<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=109226691&amp;loc=d3e2941-110230<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainLossOnDispositionOfAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainsLossesOnExtinguishmentOfDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Difference between the fair value of payments made and the carrying amount of debt which is extinguished prior to maturity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=126972273&amp;loc=d3e12355-112629<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126972273&amp;loc=d3e12317-112629<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainsLossesOnExtinguishmentOfDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ImpairmentOfIntangibleAssetsFinitelived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of impairment loss recognized in the period resulting from the write-down of the carrying amount of a finite-lived intangible asset to fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16373-109275<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ImpairmentOfIntangibleAssetsFinitelived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxesPaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of cash paid during the current period to foreign, federal, state, and local authorities as taxes on income.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126999549&amp;loc=d3e4297-108586<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3536-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxesPaid</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInAccountsPayable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in the aggregate amount of liabilities incurred (and for which invoices have typically been received) and payable to vendors for goods and services received that are used in an entity's business.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInAccountsPayable</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the period in the amount due for taxes based on the reporting entity's earnings or attributable to the entity's income earning process (business presence) within a given jurisdiction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInContractWithCustomerAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in right to consideration in exchange for good or service transferred to customer when right is conditioned on something other than passage of time.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInContractWithCustomerAsset</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 912<br> -SubTopic 310<br> -Section 45<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126938201&amp;loc=d3e55415-109406<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInInventories">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in the aggregate value of all inventory held by the reporting entity, associated with underlying transactions that are classified as operating activities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInInventories</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOperatingCapitalAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOperatingCapitalAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOtherCurrentLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in current liabilities classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOtherCurrentLiabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in employer-related costs classified as other and current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOtherOperatingAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in operating assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOtherOperatingAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InterestPaidNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash paid for interest, excluding capitalized interest, classified as operating activity. Includes, but is not limited to, payment to settle zero-coupon bond for accreted interest of debt discount and debt instrument with insignificant coupon interest rate in relation to effective interest rate of borrowing attributable to accreted interest of debt discount.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126999549&amp;loc=d3e4297-108586<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 17<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3367-108585<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3536-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InterestPaidNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInFinancingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow (outflow) from financing activities, including discontinued operations. Financing activity cash flows include obtaining resources from owners and providing them with a return on, and a return of, their investment; borrowing money and repaying amounts borrowed, or settling the obligation; and obtaining and paying for other resources obtained from creditors on long-term credit.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3521-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInFinancingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInInvestingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow (outflow) from investing activities, including discontinued operations. Investing activity cash flows include making and collecting loans and acquiring and disposing of debt or equity instruments and property, plant, and equipment and other productive assets.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3521-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInInvestingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInOperatingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow (outflow) from operating activities, including discontinued operations. Operating activity cash flows include transactions, adjustments, and changes in value not defined as investing or financing activities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3536-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3521-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInOperatingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization expense for right-of-use asset from operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsForHedgeFinancingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for a financial contract that meets the hedge criteria as either cash flow hedge, fair value hedge or hedge of net investment in foreign operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 27<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3581-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsForHedgeFinancingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsOfDebtIssuanceCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow paid to third parties in connection with debt origination, which will be amortized over the remaining maturity period of the associated long-term debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsOfDebtIssuanceCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to satisfy grantee's tax withholding obligation for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to acquire investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3213-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3151-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26853-111562<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquireEquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to acquire investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI), classified as investing activity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 321<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123583714&amp;loc=SL75117360-209713<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3444-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquireEquitySecuritiesFvNi</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquireIntangibleAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to acquire asset without physical form usually arising from contractual or other legal rights, excluding goodwill.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3213-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquireIntangibleAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow associated with the acquisition of long-lived, physical assets that are used in the normal conduct of business to produce goods and services and not intended for resale; includes cash outflows to pay for construction of self-constructed assets.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3213-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquirePropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the issuance of a long-term debt instrument which can be exchanged for a specified amount of another security, typically the entity's common stock, at the option of the issuer or the holder.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow from issuance of shares under share-based payment arrangement. Includes, but is not limited to, option exercised.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=SL79508275-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfWarrants">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from issuance of rights to purchase common shares at predetermined price (usually issued together with corporate debt).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfWarrants</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow from sale, maturity, prepayment and call of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3151-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3179-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26853-111562<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RealizedInvestmentGainsLosses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of realized gain (loss) on investment.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04.3(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RealizedInvestmentGainsLosses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow from the repayment of a long-term debt instrument which can be exchanged for a specified amount of another security, typically the entity's common stock, at the option of the issuer or the holder.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfSecuredDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to repay long-term debt that is wholly or partially secured by collateral. Excludes repayments of tax exempt secured debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfSecuredDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase in right-of-use asset obtained in exchange for operating lease liability.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI https://asc.fasb.org/extlink&amp;oid=123414884&amp;loc=SL77918982-209971<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
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<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical) - USD ($)<br> $ in Millions</strong></div></th>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="nump">0.00%<span></span>
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<td class="nump">0.00%<span></span>
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<td class="nump">0.00%<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1 Percent Convertible Senior Notes [Member]</a></td>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
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<td class="text">&#160;<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face (par) amount of the original debt instrument that was repurchased.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592668727568">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basis of Presentation<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2022</div></th></tr>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.&#160; Basis of Presentation</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended&#160;September 30, 2022 and 2021 on the same basis as the audited financial statements for the year ended December 31, 2021. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2021 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;).</div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for organization, consolidation and basis of presentation of financial statements disclosure.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 205<br> -URI https://asc.fasb.org/topic&amp;trid=2122149<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -URI https://asc.fasb.org/topic&amp;trid=2197479<br></p></div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592585532720">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2022</div></th></tr>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2.&#160; Significant Accounting Policies</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue Recognition</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Our Revenue Sources</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts within deferred revenue in our condensed consolidated balance sheet.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808. ASC 808 does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC 606, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span>. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We also recognize sales milestone payments and royalties we earn under our other partnerships as commercial revenue.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaborative agreements</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, research and development, or R&amp;D, services, and manufacturing services.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 6, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for collaborations with substantive changes that occurred in 2022. Additionally, see </span>Note 6, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2021 for a summary of each of our material collaborative agreements.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">1.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Identify the contract</div></td>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partner approved the contract and we are both committed to perform our obligations;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have identified our rights, our partner&#8217;s rights and the payment terms;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe collectability of the consideration is probable.</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">.</span></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Identify the performance obligations</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Often we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.</div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">3.</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Determine the transaction price</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/or are usually based on scientific progress which is inherently uncertain. For example, in the first quarter of 2022, we earned a $10 million milestone payment from Biogen when Biogen advanced the Phase 1/2 study for ION859, an investigational antisense medicine targeting leucine rich repeat kinase 2, or LRRK2, in patients with Parkinson&#8217;s disease. We did not consider the milestone payment probable until Biogen achieved the milestone event because advancing ION859 was contingent on Biogen advancing a Phase 1/2 study and was not within our control. We recognized the milestone payment in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payment.</div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">4.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Allocate the transaction price</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Next, we allocate the transaction price to each of our performance obligations. When we have to allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:</div>

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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated future product sales;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated royalties we may receive from future product sales;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated contractual milestone payments we may receive;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated expenses we may incur;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated income taxes; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A discount rate.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We typically estimate the selling price of R&amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated number of internal hours we will spend performing these services;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work we will perform;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work that we will contract with third parties to perform; and</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of API we will use.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.</div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">5.</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Recognize revenue</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize royalty revenue, including royalties from SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;A, expenses in our condensed consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Reserves for TEGSEDI and WAYLIVRA commercial revenue</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi, Sobi is responsible for any applicable reserves.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Prior to our distribution agreements with Sobi, w</span>e recorded TEGSEDI and WAYLIVRA commercial revenue at our net sales price, or transaction price. We included in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offered within contracts between us and our customers, wholesalers, distributors, health care providers and other indirect customers. We estimated our reserves using the amounts we have earned or we could claim on the associated sales. We classified our reserves as a reduction of accounts receivable when we were not required to make a payment or as a current liability when we were required to make a payment. In certain cases, our estimates included a range of possible outcomes that were probability weighted for relevant factors such as our historical experience, contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflected our best estimates under the terms of our respective contracts. When calculating our reserves and related TEGSEDI and WAYLIVRA commercial revenue, we only recognized amounts to the extent that we considered it probable that we would not have to reverse a significant amount of the cumulative sales we previously recognized in a future period. Under our agreements with Sobi, we transferred all reserves to Sobi. See our revenue recognition policy in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span>, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2021 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales prior to our agreements with Sobi.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Research and development revenue under collaboration agreements:</span></div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Upfront payments</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we enter into a collaboration agreement and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. For example, under our collaboration agreement with Roche to develop IONIS-FB-L<sub>Rx</sub> for the treatment of complement-mediated diseases, we received a $75 million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $75 million upfront payment using an input method over the estimated period of time we are providing R&amp;D services.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Milestone payments</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the second quarter of 2022, we achieved a $20 million milestone payment from Roche when we advanced the Phase 2 study in patients with dry age-related macular degeneration, or AMD, under our collaboration agreement with Roche to develop IONIS-FB-L<sub>Rx</sub>. We added this payment to the transaction price and allocated it to our R&amp;D services performance obligation for IONIS-FB-L<sub>Rx</sub>. We are recognizing revenue related to this milestone payment over our estimated period of performance. As a result, we recorded a cumulative catch-up adjustment of $13.8 million to increase revenue in the second quarter of 2022 for this payment. We estimate we will satisfy our performance obligation in the fourth quarter of 2023.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2022, we recognized $13 million in milestone payments when Biogen advanced two targets under our neurology collaborations. We concluded that these milestone payments were not related to our R&amp;D services performance obligations for these collaborations. Therefore, we recognized the milestone payments in full in the third quarter of 2022.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">License fees</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. For example, in the third quarter of 2022, we earned a $35 million license fee from Roche when Roche licensed IONIS-FB-L<sub>Rx</sub>, an investigational medicine in development to treat complement-mediated diseases.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Sublicense fees</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not have any performance obligations related to the sublicense. For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Amendments to Agreements</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:</div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the goods and/or services are sold at a stand-alone selling price.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Multiple agreements</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the agreements were negotiated together with a single objective;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the goods and/or services promised under the agreements are a single performance obligation.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: a new strategic neurology collaboration agreement and a stock purchase agreement. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis.</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Eplontersen Collaboration with AstraZeneca</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a result we had one performance obligation.&#160; For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#8217;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related to commercial and medical affairs activities as reductions of our SG&amp;A expense and R&amp;D expense, respectively. Refer to Item 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations</span>, for further details on the financial statement impacts of our eplontersen collaboration with AstraZeneca. </div>

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<div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents the amounts we have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts receivable to be unconditional. We typically receive payment within </span><span style="-sec-ix-hidden:Fact_cb46feec840d4d05b86df2a2af3b44c3">one quarter</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of billing our partner or customer</span>.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of September 30, 2022, approximately 73.1 percent of our contracts receivables were from two significant customers. As of December 31, 2021, approximately 93.8 percent of our contracts receivables were from two significant customers.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled SPINRAZA Royalties</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen for SPINRAZA royalties. We include these unbilled amounts in other current assets on our condensed consolidated balance sheet.</div>

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<div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers and receive payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue on our condensed consolidated balance sheet.</span> During the three months ended&#160;September 30, 2022 and 2021, we recognized $23.1 million and $21.1 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">During the </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recognized $</span>69.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>71.9<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. </span>For further discussion, refer to our revenue recognition policy above.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Sales</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales. </div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our accrued liabilities consisted of the following (in thousands):</div>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial expenses</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,471</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13,049</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,315</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total accrued liabilities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">128,002</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">88,560</div></td>
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  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Estimated Liability for Clinical Development Expenses</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly basis, we estimate our liability for preclinical and clinical development expenses we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these expenses. These expenses primarily relate to third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon settlement, these expenses may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, Cash Equivalents and Investments</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#8220;available-for-sale&#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our condensed consolidated statement of operations. We use the specific identification method to determine the cost of securities sold.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At September 30, 2022, we held equity investments in three publicly held companies and eight privately held companies.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our condensed consolidated statement of operations. We account for our equity investments in publicly held companies based on observable inputs such as quoted prices in active markets for identical assets. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. We recorded an immaterial amount of fair value adjustments related to our equity investments for the three and nine months ended&#160;September 30, 2022 and 2021.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventory Valuation</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or net realizable value under the first-in, first-out method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials, they have alternative future uses, which we refer to as clinical raw materials. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency. Our raw materials - commercial inventory includes API for our commercial medicines. We capitalize material, labor and overhead costs as part of our raw materials - commercial inventory.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30, 2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- clinical</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,507</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- commercial</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,139</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total raw materials</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,617</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,646</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Work in process</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,770</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">288</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">390</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,645</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,806</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Leases</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine if an arrangement contains a lease at inception of the arrangement. As of September 30, 2022, we only had operating leases. We recognize a right-of-use operating lease asset and associated short- and long-term operating lease liability on our condensed consolidated balance sheet for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we will pay over the lease term. We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal options if we concluded we were reasonably certain that we will exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease term.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commenced in January 2022 when the office space was ready for our tenant&#8217;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending in November 2028 with no option to extend the sublease. Under the sublease agreement we provided a seven-month free rent period, which commenced in January 2022. We will receive lease payments over the sublease term totaling $9.6 million. We are recognizing sublease payments as other income on a straight-line, gross basis over the term of our sublease.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility in Oceanside, California. The lessor will develop and construct a building composed of manufacturing space, office space, research and development space and warehouse space. We will design and construct tenant improvements to customize the facility&#8217;s interior space. We will lease the facility for an initial term of <span style="-sec-ix-hidden:Fact_f55efb1442234cfa8ea3fb7d8884b511">20 years and 3 months</span> with options to extend the lease for two additional terms of 10 years each. The lease will commence when the lessor's construction is complete and we are able to occupy the facility.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we concurrently entered into two purchase and sale agreements with a real estate investor. Under the agreements, we sold and leased back the facilities at our headquarters location in Carlsbad, California and will sell, subject to meeting certain closing conditions, two lots of undeveloped land adjacent to our headquarters. We sold the facilities at our headquarters for a total purchase price of $263.4 million and we expect to receive total proceeds of $33.0 million upon the close of the sale of the two lots. We used a portion of the sale proceeds to extinguish our mortgage debt on our headquarters facilities of $51.3 million. The initial lease term for our headquarters facilities is 15 years with options to extend the lease for two additional terms of five years each. In connection with the sale of our two undeveloped lots, we will enter into a build-to-suit lease agreement with the same real estate investor who will build a new R&amp;D facility for us on those lots. Once this new facility is completed, our lease will commence.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Patent Expenses</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our condensed consolidated balance sheet and we expense them as the services are provided.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the U.S. Patent and Trademark Office, or foreign equivalent, issues the patent. </span>We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes. Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the provision for income taxes in the period in which we make such determination.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Long-lived Assets</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate long-lived assets, which include property, plant and equipment, right-of-use assets and patent costs, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Use of Estimates</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the </span>U.S. that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Loss Per Share</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>

<div><br/></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our basic net loss per share for the three and nine months ended&#160;September 30, 2022 and 2021 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Our basic net loss per share for the three months ended September 30, 2022 and 2021 were $0.33 and $0.58, respectively. Our basic net loss per share for the nine months ended&#160;September 30, 2022 and 2021 were $1.53 and $1.80, respectively.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Diluted net loss per share</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three and nine months ended&#160;September 30, 2022 and 2021, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:</div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent convertible senior notes, or 0% Notes;</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the 0% Notes;</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent convertible senior notes, or 0.125% Notes;</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the 0.125% Notes;</div></td>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested performance restricted stock units, or PRSUs; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Stock Purchase Plan, or ESPP.</div></td>
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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three and nine months ended&#160;September 30, 2021, common stock that we could have issued from our 1 percent convertible senior notes, or 1% Notes, would also have had an anti-dilutive effect on net loss per share.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally as of September 30, 2022, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Derivatives and Hedging</span>, or ASC 815, and our convertible debt instruments were not issued at a substantial premium. We record the entire debt issuance costs as a contra-liability in our condensed consolidated balance sheet at issuance and we amortize them over the contractual term using an updated effective interest rate. As such, the ending balances for our 0% and 0.125% Notes represent the principal balance of each convertible debt instrument less debt issuance costs. We amortize debt issuance costs for our 0% and 0.125% Notes over the respective contractual term using an effective interest rate of 0.5 percent for each note. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Convertible Debt</span>, for further details on our convertible debt instruments.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Call Spread</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the issuance of our 0% Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not meet the definition of a liability using the guidance contained in ASC Topic 480, therefore we account for the note hedges and warrants using the Derivatives and Hedging &#8211; Contracts in Entity&#8217;s Own Equity accounting guidance contained in ASC 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified in shareholders&#8217; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our condensed consolidated balance sheet. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Segment Information</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We operate as a <span style="-sec-ix-hidden:Fact_ba6a4e8bb35940dbbf919d263b57d70e">single</span> segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-based Compensation Expense</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On the grant date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the awards, and actual and projected employee stock option exercise behaviors.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or 2020 Plan. As a result, all employees are now under an Ionis stock plan and subject to the same Black-Scholes assumptions.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the nine months ended&#160;September 30, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Options:</div>

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    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
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  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">*</td>
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  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Board of Director Stock Options:</div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.4 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.3 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">ESPP:</div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RSU&#8217;s:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. The RSUs we granted after June 2020 to our board of directors fully vest after one year. The weighted-average grant date fair value of RSUs granted to employees and our board of directors for the nine months ended&#160;September 30, 2022 were $34.88 and $38.06 per share, respectively.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PRSU&#8217;s:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added PRSU awards to the compensation for our other Section 16 officers. Under the terms of the grants, <span style="-sec-ix-hidden:Fact_3ea144f70898401099a1731ad0c7e39f"><span style="-sec-ix-hidden:Fact_b531c97d5a394e3f8a5454ecd82ddb93"><span style="-sec-ix-hidden:Fact_b2b6dbe875764e78b9cce0b8464216dd">one third</span></span></span> of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero percentto 150 percent of the target number depending on our relative TSR.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to our Section 16 officers for the nine months ended&#160;September 30, 2022 and 2021 were $42.28 and $77.17 per share, respectively.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the three and nine months ended&#160;September 30, 2022 and 2021 (in thousands).</div>

<div><br/></div>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">98,419</div></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of September 30, 2022, total unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $50.9 million, $53.0 million and $3.4 million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures. We expect to recognize the cost of stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.2 years, 1.4 years and 1.1 years, respectively. Our stock-based compensation expense related to equity awards decreased in the three and nine months ended September 30, 2022 compared to the same periods in 2021 due to decreased headcount of longer-tenured employees as a result of restructuring our commercial operations for TEGSEDI and WAYLIVRA.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Recently Adopted Accounting Standards</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2022, the Financial Accounting Standards Board, or FASB, issued clarifying guidance on fair value measurement of equity securities subject to contractual trading restrictions. The guidance clarifies that contractual trading restrictions are not considered part of the unit of account of equity securities and therefore, are not considered when measuring the fair value of equity securities. This update is effective for interim and annual periods beginning January 1, 2024 on a prospective basis. Early adoption of this guidance is permitted at an interim or annual period. We early adopted this new guidance in the third quarter of 2022. This guidance did not have an impact on our condensed consolidated financial statements.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any other recently issued accounting standards to have a material impact to our financial results.</div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592585556480">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2022</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsAbstract', window );"><strong>Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentTextBlock', window );">Investments</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3.&#160; Investments</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2022:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">One year</span> or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">one year</span> but within <span style="text-indent: 0pt;">two years</span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">two years</span> but within <span style="text-indent: 0pt;"><span style="-sec-ix-hidden:Fact_f12cc57cfa544d218ac6c26f9aae5797">three and a half years</span></span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As illustrated above, at September 30, 2022, 97 percent of our available-for-sale securities had a maturity of less than two years.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All of our available-for-sale debt securities are available to us for use in our current operations. As a result, we categorize all of these securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date. This reflects our intention to use the proceeds from the sale of these investments to fund our operations, as necessary.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We invest in available-for-sale securities</span> with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard &amp; Poor&#8217;s, or S&amp;P, Moody&#8217;s or Fitch, respectively.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At September 30, 2022, we had an equity ownership interest of less than 20 percent in eight private companies and three public companies with which we conduct business.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>

<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;">Amortized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">September 30, 2022</span></div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Available-for-sale securities:</span></div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">487,666</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,327</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">482,340</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,987</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,686</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">103,313</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">462,475</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,761</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">458,736</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,059</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(797</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,262</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">258,362</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(12,654</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">245,714</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,987</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,541</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,454</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">298,431</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,247</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">292,197</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,591</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(540</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,053</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">600,371</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">29</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(20,982</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">579,418</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,733,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,701,033</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,097</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,841</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,256</div></td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40,372</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38,212</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,257</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,841</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47,628</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,771,810</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,321</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(40,470</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
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<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Available-for-sale securities:</span></div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">383,870</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">728</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">384,372</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48,493</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <tr>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">379,687</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,935</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,374</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,635</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(500</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,274</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,909</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(224</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,686</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,136</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(37</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">638,615</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,966</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">635,120</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,251,172</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,248,124</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,145</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(837</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,205</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Privately held equity securities included in deposits and other assets (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,615</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,707</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,322</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,512</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,852</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(837</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50,527</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,278,684</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,115</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,148</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,298,651</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Includes investments classified as cash equivalents in our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the nine months ended&#160;September 30, 2022, we recognized a $10.9 million unrealized non-cash loss in our condensed consolidated statement of operations related to a decrease in the fair value of our investments in publicly traded companies.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at</span> cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div></td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments we consider to be temporarily impaired at September 30, 2022 (in thousands, except for number of investments).</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,084</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">725,008</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(17,981</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69,640</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(875</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53,299</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">122,939</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,227</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">643,231</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(8,327</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52,767</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,681</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">695,998</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,008</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40,160</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(658</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase rather than underlying credit deterioration for any of the issuers. We believe it is more likely than not that we will be able to hold our debt securities with declines in value to maturity. Therefore, we anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592586844368">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fair Value Measurements<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2022</div></th></tr>
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<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4.&#160; Fair Value Measurements</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1, defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly held biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions, which includes our investments in equity securities in privately held biotechnology companies. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at September 30, 2022 and December 31, 2021 that we regularly measure and carry at fair value. As of December 31, 2021, one of <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">our investments in publicly held biotechnology companies was subject to trading restrictions that ended in the third quarter of 2022; as a result, we included a lack of marketability discount in valuing this investment, which is a Level 3 input.</span> The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</div>

<div><br/></div>

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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">750,933</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">85,315</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">85,315</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,964</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,964</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets</div></div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,256</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,256</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 8pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2021</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
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  </tr>
  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182,634</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182,634</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (5)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,464</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,464</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,099</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,099</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,205</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,875</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</div></div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,807,528</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">727,708</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,065,490</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following footnotes reference lines in our condensed consolidated balance sheet:</div>

<div><br/></div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in cash and cash equivalents in our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$23.5 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in short-term investments.</div></td>
  </tr>
</table>

<div><br/></div>

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  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$10.0 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.</div></td>
  </tr>
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<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$2.3 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.</div></td>
  </tr>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Convertible Notes</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our 0.125% Notes and 0% Notes had a fair value of $498.7 million and $631.8 million at September 30, 2022, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.</div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592585752960">
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<th class="th" colspan="1">9 Months Ended</th>
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<td class="text">&#160;<span></span>
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<div style="text-align: left; text-indent: -45pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#160; Income Taxes</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2022, the Tax Cuts and Jobs Act of 2017, or TCJA, requires taxpayers to amortize research and development expenditures over five years pursuant to Internal Revenue Code, or IRC, Section 174. Although the U.S. Congress is considering legislation that would defer the amortization requirement to later years, we have no assurance that the provision will be repealed or otherwise modified. Since we expect taxable income in 2022, we recorded income tax expense of $0.3 million and $3.6 million for the three months and nine months ended September 30, 2022, respectively, compared to income tax benefit of $1.3 million and $0.9 million for the same periods in 2021.</div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for income taxes. Disclosures may include net deferred tax liability or asset recognized in an enterprise's statement of financial position, net change during the year in the total valuation allowance, approximate tax effect of each type of temporary difference and carryforward that gives rise to a significant portion of deferred tax liabilities and deferred tax assets, utilization of a tax carryback, and tax uncertainties information.</p></div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592585529488">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2022</div></th></tr>
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<td class="text">&#160;<span></span>
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<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6.&#160; Collaborative Arrangements and Licensing Agreements</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Below, we have included our Biogen, Roche and Bayer collaborations, which are our only collaborations with substantive changes during </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2022</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, 2021</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

<div><br/></div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Strategic Partnership</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Biogen</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#8217;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. We and Biogen are currently developing numerous investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, SMA, Angelman Syndrome, Alzheimer&#8217;s disease<sub>&#160;</sub>and Parkinson&#8217;s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through September 30, 2022, we have received $3.4 billion from our Biogen collaborations.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>

<div><br/></div>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71</div></td>
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  </tr>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our condensed consolidated balance sheet at September 30, 2022 and December 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>included deferred revenue of $360.2 million and $407.5 million, respectively, related to our relationship with Biogen.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2022, we earned $13 million in milestone payments from Biogen when Biogen advanced two targets under our neurology collaborations. We recognized one of these milestone payments in full in the third quarter of 2022 because we did not have any remaining performance obligations related to the milestone payment. We added the other payment to the transaction price and allocated it to our R&amp;D services performance obligation for the 2012 neurology collaboration. We are recognizing revenue for our R&amp;D services performance obligation over our estimated period of performance. We will achieve the next payment of up to $10 million if Biogen advances another medicine under our 2013 strategic neurology collaboration.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Roche</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have two collaborations with Roche, one to develop <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-FB-L</span><sub>Rx</sub> for the treatment of complement-mediated diseases, and one to <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">develop </span>treatments for Huntington's disease, or HD.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In October 2018, we entered into a collaboration agreement with Roche to develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We are currently conducting Phase 2 studies in </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> disease indications for IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of patients with geographic atrophy, or GA, the advanced stage of dry AMD, and a </span><span style="-sec-ix-hidden:Fact_37bb84ab38b14330b8b82ce65b069cf8">second</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of patients with immunoglobulin A nephropathy, or IgAN. After positive data from a Phase 2 clinical study, Roche licensed IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in July 2022 for $</span>35<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and </span>plans to advance <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-FB-L</span><sub>Rx</sub> into Phase 3 development for patients with IgAN<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. As a result, Roche is responsible for global development, regulatory and commercialization activities and costs for the Phase 3 IgAN study of IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We will continue to lead and conduct the open label Phase 2 study in patients with IgAN and the Phase 2 study in patients with GA</span>. In July 2022, we amended our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-FB-L</span><sub>Rx</sub> collaboration agreement with Roche. The amendment changed future potential milestone payments we could receive under the collaboration. We determined there were no changes that would require adjustments to revenue we previously recognized. Under our amended collaboration agreement, we are eligible to receive up to $145 million in development milestones, $279 million in regulatory milestones and $280 million in sales-related milestone payments. In addition, we are also eligible to receive tiered royalties from the high teens to 20 percent on net sales.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the collaboration agreement with Roche to develop treatments for HD, we discovered and developed tominersen, an investigational medicine targeting huntingtin, or HTT, protein, through completion of our Phase 1/2 clinical study in people with early stage HD. In the fourth quarter of 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. Roche is responsible for all global development, regulatory and commercialization activities and costs for tominersen. In March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest HD based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded iDMC. In January 2022, Roche announced it is actively preparing to initiate a new Phase 2 study of tominersen in patients with HD. Post-hoc analyses from the GENERATION HD1 study suggested tominersen may benefit younger adult patients with lower disease burden. From inception through September 30, 2022, we have received $283 million from our Roche collaborations.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2022 and 2021, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our condensed consolidated balance sheet at September 30, 2022 and December 31, 2021 included deferred revenue of $23.6 million and $31.6 million, respectively, related to our relationship with Roche.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed above, in the third quarter of 2022, we earned a $35 million payment from Roche when Roche licensed IONIS-FB-L<sub>Rx</sub>. We recognized the license fee as revenue in the third quarter of 2022 because Roche had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Roche. We will achieve the next payment of up to $90 million if Roche advances a medicine under our IONIS-FB-L<sub>Rx</sub> collaboration.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Bayer</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI<sub>Rx</sub> for the prevention of thrombosis. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI<sub>Rx</sub>, initiate development of fesomersen, an investigational LIgand-Conjugated Antisense medicine we designed to inhibit the production of Factor XI, and license fesomersen to Bayer. In the fourth quarter of 2022, Bayer communicated to us that it will discontinue the clinical development program for fesomersen and return fesomersen to us. We have received over $190 million from Bayer over the term of this collaboration.</div>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Convertible Debt<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7. Convertible Debt</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0 Percent</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Convertible Senior Notes and Call Spread</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we completed a $632.5 million offering of convertible senior notes. We used a portion of the net proceeds from the issuance of the 0% Notes to repurchase $247.9 million in principal of our 1% Notes for $257.0 million.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At September 30, 2022, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes outstanding (amounts in millions except interest rate and price per share data):</div>

<div><br/></div>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde">April 2026</span></div></td>
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.84</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
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    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.39</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
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    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% Notes by increasing the effective conversion price on our 0% Notes. We increased our effective conversion price to $76.39 with the same number of underlying shares as our 0% Notes. The call spread cost us $46.9 million, of which $136.7 million was for the note hedge purchase, offset by $89.8 million we received for selling the warrants. Similar to our 0% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the 0% Notes. The note hedges will expire upon maturity of the 0% Notes, or April 2026. The note hedges and warrants are separate transactions and are not part of the terms of our 0% Notes. The holders of the 0% Notes do not have any rights with respect to the note hedges and warrants.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our condensed consolidated balance sheet. See our Call Spread accounting policy in Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, in the Notes to the Condensed Consolidated Financial Statements. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">0.125 Percent Convertible Senior Notes and Call Spread</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At September 30, 2022, we had the following 0.125% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):</div>

<div><br/></div>

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    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">0.125% Notes</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">548.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec">December 2024</span></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
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    <td style="vertical-align: top;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
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    <td colspan="2" style="vertical-align: top;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent</div></td>
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    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5 percent</div></td>
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    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83.28</div></td>
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    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">123.38</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In conjunction with the issuance of our </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes in December 2019, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our </span>0.125% Notes by increasing the effective conversion price on our 0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We increased our effective conversion price to $</span>123.38<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> with the same number of underlying shares as our </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes. The call spread cost us $</span>52.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, of which $</span>108.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million was for the note hedge purchase, offset by $</span>56.1<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we received for selling the warrants. Similar to our </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The note hedges will expire upon maturity of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The holders of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> do not have any rights with respect to the note hedges and warrants.</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our condensed consolidated balance sheet. See our Call Spread accounting policy in Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, in the Notes to the Condensed Consolidated Financial Statements. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1 Percent Convertible Senior Notes</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we repurchased $247.9 million in aggregate principal amount of our 1% Notes in privately negotiated transactions. As a result of the repurchase, we recognized an $8.6 million loss on early retirement of debt in the second quarter of 2021, reflecting the early retirement of a significant portion of our 1% Notes. The loss on the early retirement of our debt is the difference between the amount paid to retire our 1% Notes and the net carrying balance of the liability at the time that we retired the debt. We paid the remaining principal balance of our 1% Notes with $62.0 million of cash at maturity in November 2021.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Other Terms of Convertible Senior Notes</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The </span>0%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to </span>100 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.</span> The 1% Notes were subject to similar terms.</div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592585752960">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Legal Proceedings<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2022</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommitmentsAndContingenciesDisclosureAbstract', window );"><strong>Legal Proceedings [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LegalMattersAndContingenciesTextBlock', window );">Legal Proceedings</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8. Legal Proceedings</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On </span>August 5, 2021,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>four<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> purported former stockholders of Akcea filed an action in the Delaware Court of Chancery captioned John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al., C.A. </span>No<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>2021-0681<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or the Delaware Action. The plaintiffs in the Delaware Action asserted claims against (i) former members of Akcea&#8217;s board of directors; and (ii) Ionis, or collectively, the Defendants. The plaintiffs asserted putatively direct claims on behalf of a purported class of former Akcea stockholders. The plaintiffs in the Delaware Action asserted that the Defendants breached their fiduciary duties in connection with the </span>October 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> take-private transaction that Ionis and Akcea entered into, in which Akcea became a wholly-owned subsidiary of Ionis. We believe this lawsuit is without merit. However, the outcome of this lawsuit or any other lawsuit that may be filed challenging the </span>October 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> take-private transaction is uncertain. Accordingly, on </span>June 3, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the parties reached an agreement in principle to settle the Delaware Action for $</span>12.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. A Stipulation and Agreement of Compromise, Settlement and Release, or the Stipulation and Settlement Agreement reflecting the terms of the proposed settlement was executed and filed with the Delaware Court of Chancery on </span>July 5, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. On </span>October 11, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the Delaware Court of Chancery entered an Order and Final Judgment, or the Order, approving the Stipulation and Settlement Agreement in full after determining that the Stipulation and Settlement Agreement was fair, reasonable, and adequate. The Order provides for the full settlement, satisfaction, compromise and release of all claims that were asserted in the Delaware Action. The Order contains </span>no<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> admission of wrongdoing on the part of any of the Defendants. We recorded a legal reserve of $</span>12.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and the corresponding litigation settlement expense within other expense in the accompanying condensed consolidated statements of operations in the </span>second<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span>2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the proposed litigation settlement. In </span>the third quarter of 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we received insurance contributions toward the settlement in the amount of $</span>4.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million from our insurance carriers. We recorded the insurance contributions as a reduction to the litigation settlement expense in the </span>third<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span>2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On </span>January 19, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, a purported stockholder of Ionis filed a stockholder derivative complaint in the Delaware Court of Chancery captioned Leo Shumacher, et al. v. Joseph Loscalzo, et al., C.A. </span>No<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>2022-0059<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or the Shumacher Action. The complaint names Ionis' board of directors, or the Board, as defendants and names Ionis as a nominal defendant. The Shumacher Action Plaintiff asserts a breach of fiduciary duty claim against the Board for awarding and receiving allegedly excessive compensation. The Shumacher Action Plaintiff also asserts an unjust enrichment claim against the non-executive directors as a result of the compensation they received. The complaint seeks, among other things, damages, restitution, attorneys&#8217; fees and costs, and such other relief as deemed just and proper by the court. On </span>March 18, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we and the Board moved to dismiss the complaint. On </span>May 24, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the parties entered into a Stipulation and Agreement of Compromise, Settlement and Release.</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On </span>May 25, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, another purported stockholder of Ionis filed a stockholder derivative complaint also in the Delaware Court of Chancery captioned Robert S. Cohen, et al. v. Joseph Loscalzo, et al., C.A. </span>No<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>2022-0453<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or the Cohen Action. The complaint names the Board as defendants and names Ionis as a nominal defendant. The Cohen Action Plaintiff asserts claims for breach of fiduciary duty, unjust enrichment, aiding and abetting breaches of fiduciary duty, and waste against the Board for awarding and receiving allegedly excessive non-executive director compensation for the years </span>2018, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, and </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. On </span>June 2, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the Cohen Action Plaintiff filed a motion to consolidate the related Cohen Action and Shumacher Action. On </span>July 5, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the Court denied the motion to consolidate in favor of the settlement pending in the Shumacher Action.</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On July 18, 2022, we filed a Form 8-K disclosing the pending settlement and attaching the Notice of Pendency of Settlement of Action. On September 21, 2022, the Court held a hearing to consider whether the terms of the settlement should be approved, at which hearing the Cohen Action plaintiff objected to the settlement. At the conclusion of the hearing, the Court declined to approve the settlement and directed the parties to meet and confer on the issue of the scope of the release. We and our Board have denied, and continue to deny, any and all allegations of wrongdoing or liability asserted in the Shumacher and Cohen Actions.</div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for legal proceedings, legal contingencies, litigation, regulatory and environmental matters and other contingencies.</p></div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592585565360">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basis of Presentation (Policies)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<td class="text">&#160;<span></span>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended&#160;September 30, 2022 and 2021 on the same basis as the audited financial statements for the year ended December 31, 2021. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2021 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;).</div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for basis of accounting, or basis of presentation, used to prepare the financial statements (for example, US Generally Accepted Accounting Principles, Other Comprehensive Basis of Accounting, IFRS).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy regarding (1) the principles it follows in consolidating or combining the separate financial statements, including the principles followed in determining the inclusion or exclusion of subsidiaries or other entities in the consolidated or combined financial statements and (2) its treatment of interests (for example, common stock, a partnership interest or other means of exerting influence) in other entities, for example consolidation or use of the equity or cost methods of accounting. The accounting policy may also address the accounting treatment for intercompany accounts and transactions, noncontrolling interest, and the income statement treatment in consolidation for issuances of stock by a subsidiary.</p></div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592581675552">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies (Policies)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2022</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccountingPoliciesAbstract', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue Recognition</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Our Revenue Sources</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts within deferred revenue in our condensed consolidated balance sheet.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808. ASC 808 does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC 606, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span>. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We also recognize sales milestone payments and royalties we earn under our other partnerships as commercial revenue.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaborative agreements</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, research and development, or R&amp;D, services, and manufacturing services.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 6, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for collaborations with substantive changes that occurred in 2022. Additionally, see </span>Note 6, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2021 for a summary of each of our material collaborative agreements.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>

<div><br/></div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">1.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Identify the contract</div></td>
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<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div>

<div><br/></div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partner approved the contract and we are both committed to perform our obligations;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have identified our rights, our partner&#8217;s rights and the payment terms;</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe collectability of the consideration is probable.</div></td>
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<div><br/></div>

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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">.</span></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Identify the performance obligations</div></td>
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<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Often we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.</div>

<div><br/></div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">3.</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Determine the transaction price</div></td>
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<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/or are usually based on scientific progress which is inherently uncertain. For example, in the first quarter of 2022, we earned a $10 million milestone payment from Biogen when Biogen advanced the Phase 1/2 study for ION859, an investigational antisense medicine targeting leucine rich repeat kinase 2, or LRRK2, in patients with Parkinson&#8217;s disease. We did not consider the milestone payment probable until Biogen achieved the milestone event because advancing ION859 was contingent on Biogen advancing a Phase 1/2 study and was not within our control. We recognized the milestone payment in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payment.</div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">4.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Allocate the transaction price</div></td>
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<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Next, we allocate the transaction price to each of our performance obligations. When we have to allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:</div>

<div><br/></div>

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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated future product sales;</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated royalties we may receive from future product sales;</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated contractual milestone payments we may receive;</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated expenses we may incur;</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated income taxes; and</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A discount rate.</div></td>
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<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We typically estimate the selling price of R&amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</div>

<div><br/></div>

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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated number of internal hours we will spend performing these services;</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work we will perform;</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work that we will contract with third parties to perform; and</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of API we will use.</div></td>
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<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.</div>

<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/></div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">5.</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Recognize revenue</div></td>
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<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize royalty revenue, including royalties from SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;A, expenses in our condensed consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Reserves for TEGSEDI and WAYLIVRA commercial revenue</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi, Sobi is responsible for any applicable reserves.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Prior to our distribution agreements with Sobi, w</span>e recorded TEGSEDI and WAYLIVRA commercial revenue at our net sales price, or transaction price. We included in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offered within contracts between us and our customers, wholesalers, distributors, health care providers and other indirect customers. We estimated our reserves using the amounts we have earned or we could claim on the associated sales. We classified our reserves as a reduction of accounts receivable when we were not required to make a payment or as a current liability when we were required to make a payment. In certain cases, our estimates included a range of possible outcomes that were probability weighted for relevant factors such as our historical experience, contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflected our best estimates under the terms of our respective contracts. When calculating our reserves and related TEGSEDI and WAYLIVRA commercial revenue, we only recognized amounts to the extent that we considered it probable that we would not have to reverse a significant amount of the cumulative sales we previously recognized in a future period. Under our agreements with Sobi, we transferred all reserves to Sobi. See our revenue recognition policy in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span>, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2021 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales prior to our agreements with Sobi.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Research and development revenue under collaboration agreements:</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Upfront payments</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we enter into a collaboration agreement and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. For example, under our collaboration agreement with Roche to develop IONIS-FB-L<sub>Rx</sub> for the treatment of complement-mediated diseases, we received a $75 million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $75 million upfront payment using an input method over the estimated period of time we are providing R&amp;D services.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Milestone payments</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the second quarter of 2022, we achieved a $20 million milestone payment from Roche when we advanced the Phase 2 study in patients with dry age-related macular degeneration, or AMD, under our collaboration agreement with Roche to develop IONIS-FB-L<sub>Rx</sub>. We added this payment to the transaction price and allocated it to our R&amp;D services performance obligation for IONIS-FB-L<sub>Rx</sub>. We are recognizing revenue related to this milestone payment over our estimated period of performance. As a result, we recorded a cumulative catch-up adjustment of $13.8 million to increase revenue in the second quarter of 2022 for this payment. We estimate we will satisfy our performance obligation in the fourth quarter of 2023.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2022, we recognized $13 million in milestone payments when Biogen advanced two targets under our neurology collaborations. We concluded that these milestone payments were not related to our R&amp;D services performance obligations for these collaborations. Therefore, we recognized the milestone payments in full in the third quarter of 2022.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">License fees</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. For example, in the third quarter of 2022, we earned a $35 million license fee from Roche when Roche licensed IONIS-FB-L<sub>Rx</sub>, an investigational medicine in development to treat complement-mediated diseases.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Sublicense fees</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not have any performance obligations related to the sublicense. For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Amendments to Agreements</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:</div>

<div><br/></div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the goods and/or services are sold at a stand-alone selling price.</div></td>
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<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Multiple agreements</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the agreements were negotiated together with a single objective;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the goods and/or services promised under the agreements are a single performance obligation.</div></td>
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<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: a new strategic neurology collaboration agreement and a stock purchase agreement. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis.</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Eplontersen Collaboration with AstraZeneca</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a result we had one performance obligation.&#160; For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#8217;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related to commercial and medical affairs activities as reductions of our SG&amp;A expense and R&amp;D expense, respectively. Refer to Item 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations</span>, for further details on the financial statement impacts of our eplontersen collaboration with AstraZeneca. </div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ReceivablesPolicyTextBlock', window );">Contracts Receivable</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents the amounts we have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts receivable to be unconditional. We typically receive payment within </span><span style="-sec-ix-hidden:Fact_cb46feec840d4d05b86df2a2af3b44c3">one quarter</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of billing our partner or customer</span>.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of September 30, 2022, approximately 73.1 percent of our contracts receivables were from two significant customers. As of December 31, 2021, approximately 93.8 percent of our contracts receivables were from two significant customers.</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy', window );">Unbilled SPINRAZA Royalties</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled SPINRAZA Royalties</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen for SPINRAZA royalties. We include these unbilled amounts in other current assets on our condensed consolidated balance sheet.</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueRecognitionPolicyTextBlock', window );">Deferred Revenue</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers and receive payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue on our condensed consolidated balance sheet.</span> During the three months ended&#160;September 30, 2022 and 2021, we recognized $23.1 million and $21.1 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">During the </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>September 30, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recognized $</span>69.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>71.9<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. </span>For further discussion, refer to our revenue recognition policy above.</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostOfSalesPolicyTextBlock', window );">Cost of Sales</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Sales</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales. </div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ResearchDevelopmentAndComputerSoftwarePolicyTextBlock', window );">Estimated Liability for Clinical Development Costs</a></td>
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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Estimated Liability for Clinical Development Expenses</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly basis, we estimate our liability for preclinical and clinical development expenses we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these expenses. These expenses primarily relate to third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon settlement, these expenses may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentPolicyTextBlock', window );">Cash, Cash Equivalents and Investments</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, Cash Equivalents and Investments</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#8220;available-for-sale&#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our condensed consolidated statement of operations. We use the specific identification method to determine the cost of securities sold.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At September 30, 2022, we held equity investments in three publicly held companies and eight privately held companies.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our condensed consolidated statement of operations. We account for our equity investments in publicly held companies based on observable inputs such as quoted prices in active markets for identical assets. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. We recorded an immaterial amount of fair value adjustments related to our equity investments for the three and nine months ended&#160;September 30, 2022 and 2021.</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryPolicyTextBlock', window );">Inventory Valuation</a></td>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventory Valuation</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or net realizable value under the first-in, first-out method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials, they have alternative future uses, which we refer to as clinical raw materials. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency. Our raw materials - commercial inventory includes API for our commercial medicines. We capitalize material, labor and overhead costs as part of our raw materials - commercial inventory.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30, 2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- clinical</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,507</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- commercial</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,139</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total raw materials</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,617</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,646</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Work in process</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,740</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,770</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">288</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">390</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,645</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,806</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeLeasesPolicyTextBlock', window );">Leases</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Leases</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine if an arrangement contains a lease at inception of the arrangement. As of September 30, 2022, we only had operating leases. We recognize a right-of-use operating lease asset and associated short- and long-term operating lease liability on our condensed consolidated balance sheet for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we will pay over the lease term. We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal options if we concluded we were reasonably certain that we will exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease term.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commenced in January 2022 when the office space was ready for our tenant&#8217;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending in November 2028 with no option to extend the sublease. Under the sublease agreement we provided a seven-month free rent period, which commenced in January 2022. We will receive lease payments over the sublease term totaling $9.6 million. We are recognizing sublease payments as other income on a straight-line, gross basis over the term of our sublease.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility in Oceanside, California. The lessor will develop and construct a building composed of manufacturing space, office space, research and development space and warehouse space. We will design and construct tenant improvements to customize the facility&#8217;s interior space. We will lease the facility for an initial term of <span style="-sec-ix-hidden:Fact_f55efb1442234cfa8ea3fb7d8884b511">20 years and 3 months</span> with options to extend the lease for two additional terms of 10 years each. The lease will commence when the lessor's construction is complete and we are able to occupy the facility.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we concurrently entered into two purchase and sale agreements with a real estate investor. Under the agreements, we sold and leased back the facilities at our headquarters location in Carlsbad, California and will sell, subject to meeting certain closing conditions, two lots of undeveloped land adjacent to our headquarters. We sold the facilities at our headquarters for a total purchase price of $263.4 million and we expect to receive total proceeds of $33.0 million upon the close of the sale of the two lots. We used a portion of the sale proceeds to extinguish our mortgage debt on our headquarters facilities of $51.3 million. The initial lease term for our headquarters facilities is 15 years with options to extend the lease for two additional terms of five years each. In connection with the sale of our two undeveloped lots, we will enter into a build-to-suit lease agreement with the same real estate investor who will build a new R&amp;D facility for us on those lots. Once this new facility is completed, our lease will commence.</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpensePolicy', window );">Research and Development Expenses</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our condensed consolidated balance sheet and we expense them as the services are provided.</div>
<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IntangibleAssetsFiniteLivedPolicy', window );">Patent Expenses</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the U.S. Patent and Trademark Office, or foreign equivalent, issues the patent. </span>We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxPolicyTextBlock', window );">Income Taxes</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes. Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the provision for income taxes in the period in which we make such determination.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.</div>
<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock', window );">Long-Lived Assets</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Long-lived Assets</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate long-lived assets, which include property, plant and equipment, right-of-use assets and patent costs, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.</div>
<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UseOfEstimates', window );">Use of Estimates</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Use of Estimates</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the </span>U.S. that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.</div>
<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerSharePolicyTextBlock', window );">Basic and Diluted Net Loss per Share</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Loss Per Share</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our basic net loss per share for the three and nine months ended&#160;September 30, 2022 and 2021 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Our basic net loss per share for the three months ended September 30, 2022 and 2021 were $0.33 and $0.58, respectively. Our basic net loss per share for the nine months ended&#160;September 30, 2022 and 2021 were $1.53 and $1.80, respectively.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Diluted net loss per share</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three and nine months ended&#160;September 30, 2022 and 2021, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:</div>

<div><br/></div>

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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent convertible senior notes, or 0% Notes;</div></td>
  </tr>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the 0% Notes;</div></td>
  </tr>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent convertible senior notes, or 0.125% Notes;</div></td>
  </tr>
</table>

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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the 0.125% Notes;</div></td>
  </tr>
</table>

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  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options;</div></td>
  </tr>
</table>

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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested performance restricted stock units, or PRSUs; and</div></td>
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Stock Purchase Plan, or ESPP.</div></td>
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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three and nine months ended&#160;September 30, 2021, common stock that we could have issued from our 1 percent convertible senior notes, or 1% Notes, would also have had an anti-dilutive effect on net loss per share.</div>

<div><br/></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally as of September 30, 2022, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtPolicyTextBlock', window );">Convertible Debt</a></td>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Derivatives and Hedging</span>, or ASC 815, and our convertible debt instruments were not issued at a substantial premium. We record the entire debt issuance costs as a contra-liability in our condensed consolidated balance sheet at issuance and we amortize them over the contractual term using an updated effective interest rate. As such, the ending balances for our 0% and 0.125% Notes represent the principal balance of each convertible debt instrument less debt issuance costs. We amortize debt issuance costs for our 0% and 0.125% Notes over the respective contractual term using an effective interest rate of 0.5 percent for each note. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Convertible Debt</span>, for further details on our convertible debt instruments.</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DerivativesPolicyTextBlock', window );">Call Spread</a></td>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Call Spread</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the issuance of our 0% Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not meet the definition of a liability using the guidance contained in ASC Topic 480, therefore we account for the note hedges and warrants using the Derivatives and Hedging &#8211; Contracts in Entity&#8217;s Own Equity accounting guidance contained in ASC 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified in shareholders&#8217; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our condensed consolidated balance sheet. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SegmentReportingPolicyPolicyTextBlock', window );">Segment Information</a></td>
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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Segment Information</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We operate as a <span style="-sec-ix-hidden:Fact_ba6a4e8bb35940dbbf919d263b57d70e">single</span> segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment.</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy', window );">Stock-Based Compensation Expense</a></td>
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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-based Compensation Expense</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On the grant date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the awards, and actual and projected employee stock option exercise behaviors.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or 2020 Plan. As a result, all employees are now under an Ionis stock plan and subject to the same Black-Scholes assumptions.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the nine months ended&#160;September 30, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>

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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Options:</div>

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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
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    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
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    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
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    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life*</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.3 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">*</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the nine months ended&#160;September 30, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns. </div></td>
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<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Board of Director Stock Options:</div>

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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.2</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
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  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">ESPP:</div>

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  <tr>
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  </tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div></td>
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  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RSU&#8217;s:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. The RSUs we granted after June 2020 to our board of directors fully vest after one year. The weighted-average grant date fair value of RSUs granted to employees and our board of directors for the nine months ended&#160;September 30, 2022 were $34.88 and $38.06 per share, respectively.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PRSU&#8217;s:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added PRSU awards to the compensation for our other Section 16 officers. Under the terms of the grants, <span style="-sec-ix-hidden:Fact_3ea144f70898401099a1731ad0c7e39f"><span style="-sec-ix-hidden:Fact_b531c97d5a394e3f8a5454ecd82ddb93"><span style="-sec-ix-hidden:Fact_b2b6dbe875764e78b9cce0b8464216dd">one third</span></span></span> of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero percentto 150 percent of the target number depending on our relative TSR.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to our Section 16 officers for the nine months ended&#160;September 30, 2022 and 2021 were $42.28 and $77.17 per share, respectively.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the three and nine months ended&#160;September 30, 2022 and 2021 (in thousands).</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"/>
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    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">163</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">111</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">376</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55,315</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,979</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,941</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,094</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of September 30, 2022, total unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $50.9 million, $53.0 million and $3.4 million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures. We expect to recognize the cost of stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.2 years, 1.4 years and 1.1 years, respectively. Our stock-based compensation expense related to equity awards decreased in the three and nine months ended September 30, 2022 compared to the same periods in 2021 due to decreased headcount of longer-tenured employees as a result of restructuring our commercial operations for TEGSEDI and WAYLIVRA.</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock', window );">Recently Adopted Accounting Standards</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Recently Adopted Accounting Standards</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2022, the Financial Accounting Standards Board, or FASB, issued clarifying guidance on fair value measurement of equity securities subject to contractual trading restrictions. The guidance clarifies that contractual trading restrictions are not considered part of the unit of account of equity securities and therefore, are not considered when measuring the fair value of equity securities. This update is effective for interim and annual periods beginning January 1, 2024 on a prospective basis. Early adoption of this guidance is permitted at an interim or annual period. We early adopted this new guidance in the third quarter of 2022. This guidance did not have an impact on our condensed consolidated financial statements.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any other recently issued accounting standards to have a material impact to our financial results.</div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for finite-lived intangible assets. This accounting policy also might address: (1) the amortization method used; (2) the useful lives of such assets; and (3) how the entity assesses and measures impairment of such assets.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 926<br> -SubTopic 20<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=120154696&amp;loc=d3e54445-107959<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 920<br> -SubTopic 350<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=120155617&amp;loc=SL120155638-234783<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126899994&amp;loc=d3e18823-107790<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 920<br> -SubTopic 350<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=120155617&amp;loc=SL120155628-234783<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 920<br> -SubTopic 350<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=120155617&amp;loc=SL120155628-234783<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IntangibleAssetsFiniteLivedPolicy</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of inventory accounting policy for inventory classes, including, but not limited to, basis for determining inventory amounts, methods by which amounts are added and removed from inventory classes, loss recognition on impairment of inventories, and situations in which inventories are stated above cost.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=116847112&amp;loc=d3e4556-108314<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -URI https://asc.fasb.org/topic&amp;trid=2126998<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(b))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 912<br> -SubTopic 330<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6471895&amp;loc=d3e55923-109411<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=116847112&amp;loc=d3e4492-108314<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 270<br> -SubTopic 10<br> -Section 45<br> -Paragraph 6<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126900757&amp;loc=d3e543-108305<br><br>Reference 7: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126899994&amp;loc=d3e18823-107790<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6361739&amp;loc=d3e7789-107766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryPolicyTextBlock</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for investment in financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(3)(b))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentPolicyTextBlock</td>
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<tr>
<td><strong> Period Type:</strong></td>
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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeLeasesPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for leasing arrangement entered into by lessee.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918666-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeLeasesPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy pertaining to new accounting pronouncements that may impact the entity's financial reporting. Includes, but is not limited to, quantification of the expected or actual impact.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<tr>
<td><strong> Balance Type:</strong></td>
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</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ReceivablesPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for receivable. Includes, but is not limited to, accounts receivable and financing receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=123577603&amp;loc=d3e5033-111524<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10178-111534<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10149-111534<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10133-111534<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ReceivablesPolicyTextBlock</td>
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<tr>
<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for costs it has incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 730<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6420194&amp;loc=d3e21568-108373<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ResearchAndDevelopmentExpensePolicy</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
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<tr>
<td><strong> Balance Type:</strong></td>
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</tr>
<tr>
<td><strong> Period Type:</strong></td>
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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ResearchDevelopmentAndComputerSoftwarePolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for its research and development and computer software activities including the accounting treatment for costs incurred for (1) research and development activities, (2) development of computer software for internal use, (3) computer software to be sold, leased or otherwise marketed as a separate product or as part of a product or process and (4) in-process research and development acquired in a purchase business combination.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 50<br> -Section 25<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=16397303&amp;loc=d3e19347-109286<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 985<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6501960&amp;loc=d3e128462-111756<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 40<br> -Section 30<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=118172244&amp;loc=d3e17916-109280<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ResearchDevelopmentAndComputerSoftwarePolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for revenue from contract with customer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 17<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130561-203045<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130566-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130563-203045<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -URI https://asc.fasb.org/topic&amp;trid=49130388<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130566-203045<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130563-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=126899994&amp;loc=d3e18823-107790<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130566-203045<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 19<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130564-203045<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130566-203045<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for revenue. Includes revenue from contract with customer and from other sources.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=126899994&amp;loc=d3e18823-107790<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126899994&amp;loc=d3e18823-107790<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for segment reporting.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8864-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8864-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8864-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8864-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8864-108599<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8864-108599<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for award under share-based payment arrangement. Includes, but is not limited to, methodology and assumption used in measuring cost.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(v)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -URI https://asc.fasb.org/topic&amp;trid=2228938<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.D.2.Q6)<br> -URI https://asc.fasb.org/extlink&amp;oid=122041274&amp;loc=d3e301413-122809<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for treatment of receivables that are billable but have not been billed as of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -URI https://asc.fasb.org/topic&amp;trid=2196771<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for the use of estimates in the preparation of financial statements in conformity with generally accepted accounting principles.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6191-108592<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6161-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6143-108592<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e5967-108592<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6061-108592<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6132-108592<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e5967-108592<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592586437440">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies (Tables)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2022</div></th></tr>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30, 2022</div></td>
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    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,507</div></td>
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  </tr>
  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total raw materials</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">288</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for Stock Options</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Options:</div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life*</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.3 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">*</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the nine months ended&#160;September 30, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns. </div></td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Board of Director Stock Options:</div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.4 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.3 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for ESPP</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">ESPP:</div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock', window );">Stock-Based Compensation Expense</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the three and nine months ended&#160;September 30, 2022 and 2021 (in thousands).</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"/>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">163</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">111</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">376</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,733</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,332</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55,315</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,979</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,941</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,094</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,884</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,147</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592576498480">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments (Tables)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock', window );">Contract Maturity of Available-for-Sale Securities</a></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2022:</div>

<div><br/></div>

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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31</div></td>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>

<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/></div>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">September 30, 2022</span></div></td>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">103,313</div></td>
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  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">462,475</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,761</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">458,736</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,059</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(797</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,262</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,040</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,964</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,133,227</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">258,362</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,987</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,541</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,454</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">579,418</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,733,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,629</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,701,033</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,097</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,841</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,256</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Privately held equity securities included in deposits and other assets (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,115</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,257</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38,212</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,771,810</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">December 31, 2021</span></div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Available-for-sale securities:</span></div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">383,870</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">728</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(226</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">384,372</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48,493</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(18</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48,494</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,424</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(64</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,360</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">134,770</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(37</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">134,778</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">612,557</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">792</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(345</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">613,004</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">382,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,686</div></td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,136</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">638,615</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,145</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,205</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Privately held equity securities included in deposits and other assets (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,615</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,707</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,322</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,512</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,852</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(837</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50,527</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,278,684</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,115</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,148</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,298,651</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Includes investments classified as cash equivalents in our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

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  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the nine months ended&#160;September 30, 2022, we recognized a $10.9 million unrealized non-cash loss in our condensed consolidated statement of operations related to a decrease in the fair value of our investments in publicly traded companies.</div></td>
  </tr>
</table>

<div><br/></div>

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  <tr>
    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at</span> cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock', window );">Temporarily Impaired Investments</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments we consider to be temporarily impaired at September 30, 2022 (in thousands, except for number of investments).</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 12 Months of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">More than 12 Months of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Temporary</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impairment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Investments</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">397</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">591,245</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,897</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">133,763</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,084</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">643,231</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,681</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">695,998</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,008</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40,160</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(658</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,769</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(679</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61,929</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,337</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">994</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(12</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,970</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(64</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,964</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(76</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">644</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(20,769</div></td>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592585489344">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fair Value Measurements (Tables)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueDisclosuresAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at September 30, 2022 and December 31, 2021 that we regularly measure and carry at fair value. As of December 31, 2021, one of <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">our investments in publicly held biotechnology companies was subject to trading restrictions that ended in the third quarter of 2022; as a result, we included a lack of marketability discount in valuing this investment, which is a Level 3 input.</span> The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</div>

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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div></td>
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  </tr>
  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (3)</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120,868</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120,868</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">727,708</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,065,490</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</div></td>
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<div><br/></div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following footnotes reference lines in our condensed consolidated balance sheet:</div>

<div><br/></div>

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    <td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in cash and cash equivalents in our condensed consolidated balance sheet.</div></td>
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<div><br/></div>

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<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
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  </tr>
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<div><br/></div>

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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$10.0 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.</div></td>
  </tr>
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<div><br/></div>

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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592582226736">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements (Tables)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th"><div>Sep. 30, 2022</div></th></tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen Collaborations [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>

<div><br/></div>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue from our relationship with Biogen</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71</div></td>
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<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember', window );">Roche Collaborations [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2022 and 2021, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592580006048">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Convertible Debt (Tables)<br></strong></div></th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ConvertibleNotesDisclosureLineItems', window );"><strong>Convertible Notes [Abstract]</strong></a></td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtTableTextBlock', window );">Convertible Senior Notes</a></td>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At September 30, 2022, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes outstanding (amounts in millions except interest rate and price per share data):</div>

<div><br/></div>

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    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.0</div></td>
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    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5 percent</div></td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.84</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.39</div></td>
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    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ConvertibleNotesDisclosureLineItems', window );"><strong>Convertible Notes [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtTableTextBlock', window );">Convertible Senior Notes</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At September 30, 2022, we had the following 0.125% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">548.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec">December 2024</span></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592580869824">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Revenue Recognition (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="7">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>USD ($) </div>
<div>Target</div>
</th>
<th class="th">
<div>Jun. 30, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2018 </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($) </div>
<div>Component </div>
<div>PerformanceObligation</div>
</th>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 159,767<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 133,093<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 435,478<span></span>
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<td class="nump">$ 370,450<span></span>
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<td class="text">&#160;<span></span>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_MajorCustomersAxis=ions_BiogenIncMember', window );">Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfAgreementsWithCollaborationPartner', window );">Number of agreements | Agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology Collaboration with Biogen [Member] | ION859 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="nump">$ 10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember', window );">Collaboration to Develop IONIS-FB-L with Roche [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">35,000<span></span>
</td>
<td class="nump">$ 13,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPriceAdditions', window );">Milestone payment received and added to transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 20,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember', window );">Neurology Collaborations with Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 13,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfTargetsAdvanced', window );">Number of targets advanced | Target</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AlnylamCollaborationMember', window );">Alnylam [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 41,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationEplontersenMember', window );">Eplontersen Collaboration with AstraZeneca [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfMaterialComponents', window );">Number of material components | Component</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner', window );">Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">55.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfAgreementsWithCollaborationPartner">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of agreements entered into with the collaboration partner.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfAgreementsWithCollaborationPartner</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfMaterialComponents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of material components identified in the collaboration agreement under Accounting Standards Codification (ASC) 808, Collaborative Arrangements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfMaterialComponents</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfTargetsAdvanced">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of targets advanced under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfTargetsAdvanced</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of costs associated with the ongoing global Phase 3 development program paid by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPriceAdditions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The additional amount of consideration the Company earned under the collaboration agreement that is added to the transaction price.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPriceAdditions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI https://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_BiogenIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_MajorCustomersAxis=ions_BiogenIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_Ion859Member</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember</td>
</tr>
<tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td></td>
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<tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_AlnylamCollaborationMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationEplontersenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationEplontersenMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
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<head>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592582219424">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Contracts Receivable (Details) - Partner<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractReceivablesAbstract', window );"><strong>Contracts Receivable [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PeriodAfterBillingWhenPaymentIsReceived', window );">Period of time after billing when payment is received</a></td>
<td class="text">3 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_SignificantPartnersAbstract', window );"><strong>Significant Partners [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfSignificantCustomers', window );">Number of significant customers</a></td>
<td class="nump">2<span></span>
</td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember', window );">Contracts Receivables [Member] | Credit Concentration [Member] | Two Significant Customers [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_SignificantPartnersAbstract', window );"><strong>Significant Partners [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">73.10%<span></span>
</td>
<td class="nump">93.80%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of significant customers with which the Company does business.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfSignificantCustomers</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
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<td>na</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The time period between billing a collaboration partner for goods delivered or services performed that are due unconditionally and payment is received from the collaboration partner, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PeriodAfterBillingWhenPaymentIsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_SignificantPartnersAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractReceivablesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractReceivablesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CreditConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CreditConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_TwoSignificantCustomersMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_MajorCustomersAxis=ions_TwoSignificantCustomersMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>36
<FILENAME>R26.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<body>
<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592582500736">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Deferred Revenue (Details) - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityAbstract', window );"><strong>Deferred Revenue [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityRevenueRecognized', window );">Revenue recognized from amounts in beginning deferred revenue balance</a></td>
<td class="nump">$ 23.1<span></span>
</td>
<td class="nump">$ 21.1<span></span>
</td>
<td class="nump">$ 69.8<span></span>
</td>
<td class="nump">$ 71.9<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiabilityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiabilityRevenueRecognized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of revenue recognized that was previously included in balance of obligation to transfer good or service to customer for which consideration from customer has been received or is due.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityRevenueRecognized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>37
<FILENAME>R27.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
							function toggleNextSibling (e) {
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</head>
<body>
<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592582184048">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Significant Accounting Policies, Accrued Liabilities (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrentAbstract', window );"><strong>Accrued Liabilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AccruedClinicalDevelopmentExpenses', window );">Clinical development expenses</a></td>
<td class="nump">$ 103,635<span></span>
</td>
<td class="nump">$ 65,730<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AccruedInLicensingFeesCurrent', window );">In-licensing expenses</a></td>
<td class="nump">7,130<span></span>
</td>
<td class="nump">8,044<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AccruedCommercialExpensesCurrent', window );">Commercial expenses</a></td>
<td class="nump">4,188<span></span>
</td>
<td class="nump">2,471<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherAccruedLiabilitiesCurrent', window );">Other miscellaneous expenses</a></td>
<td class="nump">13,049<span></span>
</td>
<td class="nump">12,315<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrent', window );">Total accrued liabilities</a></td>
<td class="nump">$ 128,002<span></span>
</td>
<td class="nump">$ 88,560<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedClinicalDevelopmentExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred through that date and payable for clinical development expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AccruedClinicalDevelopmentExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedCommercialExpensesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred through that date and payable for commercial expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AccruedCommercialExpensesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedInLicensingFeesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred through that date and payable for in-licensing fees under collaboration agreements. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AccruedInLicensingFeesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred and payable, pertaining to costs that are statutory in nature, are incurred on contractual obligations, or accumulate over time and for which invoices have not yet been received or will not be rendered. Examples include taxes, interest, rent and utilities. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedLiabilitiesCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedLiabilitiesCurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherAccruedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of expenses incurred but not yet paid classified as other, due within one year or the normal operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherAccruedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
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<TYPE>XML
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<TEXT>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592585728784">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)<br></strong></div></th>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>Company</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract', window );"><strong>Cash, Cash Equivalents and Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of publicly held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">3<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of privately held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">8<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of privately-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for under the cost method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of publicly-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for at fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract</td>
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<TYPE>XML
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<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592576512208">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Significant Accounting Policies, Inventory Valuation (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryNetAbstract', window );"><strong>Inventory Valuation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryRawMaterials', window );">Raw materials</a></td>
<td class="nump">$ 16,617<span></span>
</td>
<td class="nump">$ 18,646<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryWorkInProcess', window );">Work in process</a></td>
<td class="nump">3,740<span></span>
</td>
<td class="nump">5,770<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryFinishedGoods', window );">Finished goods</a></td>
<td class="nump">288<span></span>
</td>
<td class="nump">390<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryNet', window );">Total inventory</a></td>
<td class="nump">20,645<span></span>
</td>
<td class="nump">24,806<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember', window );">Clinical [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryNetAbstract', window );"><strong>Inventory Valuation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryRawMaterials', window );">Raw materials</a></td>
<td class="nump">15,598<span></span>
</td>
<td class="nump">14,507<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PublicUtilitiesInventoryAxis=ions_CommercialRawMaterialsMember', window );">Commercial [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryNetAbstract', window );"><strong>Inventory Valuation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryRawMaterials', window );">Raw materials</a></td>
<td class="nump">$ 1,019<span></span>
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<td class="nump">$ 4,139<span></span>
</td>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryFinishedGoods">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before valuation and LIFO reserves of completed merchandise or goods expected to be sold within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after valuation and LIFO reserves of inventory expected to be sold, or consumed within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124098289&amp;loc=d3e6676-107765<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before valuation and LIFO reserves of raw materials expected to be sold, or consumed within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(4))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before valuation and LIFO reserves of merchandise or goods in the production process expected to be completed within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(3))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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</head>
<body>
<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592576461952">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Leases (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Oct. 31, 2022 </div>
<div>USD ($) </div>
<div>Option </div>
<div>Agreement </div>
<div>Lot</div>
</th>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2021 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfSecuredDebt', window );">Payment of mortgage debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 89<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember', window );">Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor', window );">Number of purchase and sale agreements entered into with real estate investor | Agreement</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeSpaceInBostonMassachusettsMember', window );">Office Space in Boston, Massachusetts [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LessorOperatingLeaseFreeRentPeriod', window );">Free rent period under sublease agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">7 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LessorOperatingLeasePaymentsToBeReceived', window );">Lease payments to be received over term of sublease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 9,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember', window );">Development Chemistry and Manufacturing Facility in Oceanside, California [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Term of operating lease</a></td>
<td class="text">20 years 3 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of operating lease extension</a></td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember', window );">Headquarters Location in Carlsbad, California [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment', window );">Proceeds from sale of property</a></td>
<td class="nump">$ 263,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfSecuredDebt', window );">Payment of mortgage debt</a></td>
<td class="nump">$ 51,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Term of operating lease</a></td>
<td class="text">15 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of operating lease extension</a></td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember', window );">Undeveloped Land in Carlsbad, California [Member] | Forecast [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment', window );">Proceeds from sale of property</a></td>
<td class="nump">$ 33,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember', window );">Undeveloped Land in Carlsbad, California [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement', window );">Number of lots of undeveloped land included in purchase and sale agreement | Lot</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of options to extend the lease under the lessee's operating leasing.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LessorOperatingLeaseFreeRentPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period of time lessor will provide free rent under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LessorOperatingLeaseFreeRentPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of lots of undeveloped land adjacent to the Company's headquarters in Carlsbad, California included in purchase and sale agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of purchase and sale agreements entered into with a real estate investor.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseRenewalTerm">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Term of lessee's operating lease renewal, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918673-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseRenewalTerm</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseTermOfContract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Term of lessee's operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918673-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseTermOfContract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
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</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LessorOperatingLeasePaymentsToBeReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lease payments to be received by lessor for operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 30<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=124258985&amp;loc=SL77919396-209981<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LessorOperatingLeasePaymentsToBeReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the sale of long-lived, physical assets that are used in the normal conduct of business to produce goods and services and not intended for resale.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3179-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfSecuredDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to repay long-term debt that is wholly or partially secured by collateral. Excludes repayments of tax exempt secured debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfSecuredDebt</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeSpaceInBostonMassachusettsMember</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592581635952">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details) - $ / shares<br></strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic and Diluted Net Loss per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net loss per share (in dollars per share)</a></td>
<td class="num">$ (0.33)<span></span>
</td>
<td class="num">$ (0.58)<span></span>
</td>
<td class="num">$ (1.53)<span></span>
</td>
<td class="num">$ (1.8)<span></span>
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<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic and Diluted Net Loss per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
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<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
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<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic and Diluted Net Loss per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic and Diluted Net Loss per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
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<td class="nump">1.00%<span></span>
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<td class="text">&#160;<span></span>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
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<td>dtr-types:percentItemType</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592582534992">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Significant Accounting Policies, Convertible Debt (Details)<br></strong></div></th>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">0.00%<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Effective interest rate for the funds borrowed under the debt agreement considering interest compounding and original issue discount or premium.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466204&amp;loc=SL6036836-161870<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28551-108399<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124429444&amp;loc=SL124452920-239629<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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</table></div>
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<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592585712704">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Segment Information (Details)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
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<tr><th class="th">
<div>Sep. 30, 2022 </div>
<div>Segment</div>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NumberOfOperatingSegments', window );">Number of operating segments</a></td>
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</tr>
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<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of operating segments. An operating segment is a component of an enterprise: (a) that engages in business activities from which it may earn revenues and incur expenses (including revenues and expenses relating to transactions with other components of the same enterprise), (b) whose operating results are regularly reviewed by the enterprise's chief operating decision maker to make decisions about resources to be allocated to the segment and assess its performance, and (c) for which discrete financial information is available. An operating segment may engage in business activities for which it has yet to earn revenues, for example, start-up operations may be operating segments before earning revenues.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8672-108599<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NumberOfOperatingSegments</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>44
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592577039024">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Stock-Based Compensation Expense (Details)<br> $ / shares in Units, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>USD ($) </div>
<div>Period </div>
<div>$ / shares </div>
<div>shares</div>
</th>
<th class="th">
<div>Sep. 30, 2021 </div>
<div>USD ($) </div>
<div>$ / shares</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 23,837<span></span>
</td>
<td class="nump">$ 30,537<span></span>
</td>
<td class="nump">$ 74,575<span></span>
</td>
<td class="nump">$ 98,419<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=us-gaap_CostOfSalesMember', window );">Cost of Sales [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">163<span></span>
</td>
<td class="nump">111<span></span>
</td>
<td class="nump">376<span></span>
</td>
<td class="nump">293<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentExpensesMember', window );">Research, Development and Patent Expense [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">17,733<span></span>
</td>
<td class="nump">23,332<span></span>
</td>
<td class="nump">55,315<span></span>
</td>
<td class="nump">71,979<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember', window );">Selling, General and Administrative Expense [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">5,941<span></span>
</td>
<td class="nump">$ 7,094<span></span>
</td>
<td class="nump">18,884<span></span>
</td>
<td class="nump">$ 26,147<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Stock Options [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions', window );">Unrecognized compensation expense related to non-vested stock options</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">50,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 50,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year 2 months 12 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Stock Options [Member] | Board of Directors [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2.90%<span></span>
</td>
<td class="nump">1.20%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">56.20%<span></span>
</td>
<td class="nump">55.90%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">7 years 4 months 24 days<span></span>
</td>
<td class="text">7 years 3 months 18 days<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Stock Options [Member] | Employees [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.90%<span></span>
</td>
<td class="nump">0.50%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">54.90%<span></span>
</td>
<td class="nump">54.30%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">6 years 3 months 18 days<span></span>
</td>
<td class="text">4 years 10 months 24 days<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member', window );">Stock Options Granted Prior to January 1, 2022 [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">7 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember', window );">Stock Options Granted on January 1, 2022 and Thereafter [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockMember', window );">ESPP [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.20%<span></span>
</td>
<td class="nump">0.10%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">50.10%<span></span>
</td>
<td class="nump">42.40%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">6 months<span></span>
</td>
<td class="text">6 months<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested units</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">53,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 53,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year 4 months 24 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Board of Directors [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share) | $ / shares</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 38.06<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Board of Directors [Member] | Minimum [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Board of Directors [Member] | Maximum [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Employees [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share) | $ / shares</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 34.88<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested units</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 3,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 3,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year 1 month 6 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Section 16 Officers [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods', window );">Number of performance periods | Period</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">3 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest', window );">Number of units guaranteed to vest (in shares) | shares</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share) | $ / shares</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 42.28<span></span>
</td>
<td class="nump">$ 77.17<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Section 16 Officers [Member] | Minimum [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Section 16 Officers [Member] | Maximum [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Section 16 Officers [Member] | One-Year Period [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">33.30%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Section 16 Officers [Member] | Two-Year Period [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">33.30%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Section 16 Officers [Member] | Three-Year Period [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">33.30%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="5"></td></tr>
<tr><td colspan="5"><table class="outerFootnotes" width="100%"><tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the nine months ended&#160;September 30, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.</td>
</tr></table></td></tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of separate performance periods under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of units guaranteed to vest under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of units guaranteed to vest under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AllocatedShareBasedCompensationExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of expense for award under share-based payment arrangement. Excludes amount capitalized.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (h)(1)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AllocatedShareBasedCompensationExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted-average period over which cost not yet recognized is expected to be recognized for award under share-based payment arrangement, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost to be recognized for nonvested award under share-based payment arrangement. Excludes share and unit options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost to be recognized for option under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationAbstract</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period over which grantee's right to exercise award under share-based payment arrangement is no longer contingent on satisfaction of service or performance condition, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days. Includes, but is not limited to, combination of market, performance or service condition.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
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<td><strong> Balance Type:</strong></td>
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<td>duration</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The estimated dividend rate (a percentage of the share price) to be paid (expected dividends) to holders of the underlying shares over the option's term.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The risk-free interest rate assumption that is used in valuing an option on its own shares.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iv)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Rate of weighted-average expected volatility for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average grant-date fair value of options granted during the reporting period as calculated by applying the disclosed option pricing methodology.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of vesting of award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period from grant date that an equity-based award expires, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Expected term of award under share-based payment arrangement, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeStatementLocationAxis=us-gaap_CostOfSalesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeStatementLocationAxis=us-gaap_CostOfSalesMember</td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentExpensesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentExpensesMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GranteeStatusAxis=srt_ExecutiveOfficerMember</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheOneMember</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheTwoMember</td>
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<td>na</td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheThreeMember</td>
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<DOCUMENT>
<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592582489328">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments, Contract Maturity of Available-for-Sale Securities (Details)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2022</div></th></tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract', window );"><strong>Contract Maturity of Available-for-Sale Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage', window );">One year or less</a></td>
<td class="nump">66.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage', window );">After one year but within two years</a></td>
<td class="nump">31.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage', window );">After two years but within three and a half years</a></td>
<td class="nump">3.00%<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage', window );">Total</a></td>
<td class="nump">100.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange1', window );">Maximum contract maturity period, range 1</a></td>
<td class="text">1 year<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange2', window );">Maximum contract maturity period, range 2</a></td>
<td class="text">2 years<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange3', window );">Maximum contract maturity period, range 3</a></td>
<td class="text">3 years 6 months<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage', window );">Percentage of available-for-sale securities with a maturity of less than two years</a></td>
<td class="nump">97.00%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature beyond one year but within two years of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature beyond two years but within three and one-half years of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate percentage of all available-for-sale debt securities, regardless of maturity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage</td>
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<td>instant</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature within one year of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature within two years of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum contract maturity period for the first range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange2">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum contract maturity period for the second range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange2</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange3">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum contract maturity period for the third range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange3</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<title></title>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592576668320">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Investments, Summary of Investments (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>USD ($) </div>
<div>Company</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsAllOtherInvestmentsAbstract', window );"><strong>Ownership Interests in Private and Public Companies [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of private companies in which there is an equity ownership interest of less than 20% | Company</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of public companies in which there is an equity ownership interest of less than 20% | Company</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,133,227<span></span>
</td>
<td class="nump">$ 612,557<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">35<span></span>
</td>
<td class="nump">792<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(11,647)<span></span>
</td>
<td class="num">(345)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,121,615<span></span>
</td>
<td class="nump">613,004<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">600,371<span></span>
</td>
<td class="nump">638,615<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">29<span></span>
</td>
<td class="nump">471<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(20,982)<span></span>
</td>
<td class="num">(3,966)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">579,418<span></span>
</td>
<td class="nump">635,120<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Available-for-sale Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,733,598<span></span>
</td>
<td class="nump">1,251,172<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">64<span></span>
</td>
<td class="nump">1,263<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(32,629)<span></span>
</td>
<td class="num">(4,311)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,701,033<span></span>
</td>
<td class="nump">1,248,124<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFVNIAbstract', window );"><strong>Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">38,212<span></span>
</td>
<td class="nump">27,512<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">17,257<span></span>
</td>
<td class="nump">23,852<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(7,841)<span></span>
</td>
<td class="num">(837)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">47,628<span></span>
</td>
<td class="nump">50,527<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract', window );"><strong>Available-for-sale and Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,771,810<span></span>
</td>
<td class="nump">1,278,684<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">17,321<span></span>
</td>
<td class="nump">25,115<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(40,470)<span></span>
</td>
<td class="num">(5,148)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,748,661<span></span>
</td>
<td class="nump">1,298,651<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">487,666<span></span>
</td>
<td class="nump">383,870<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1<span></span>
</td>
<td class="nump">728<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(5,327)<span></span>
</td>
<td class="num">(226)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">482,340<span></span>
</td>
<td class="nump">384,372<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">258,362<span></span>
</td>
<td class="nump">382,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">6<span></span>
</td>
<td class="nump">331<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(12,654)<span></span>
</td>
<td class="num">(2,644)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">245,714<span></span>
</td>
<td class="nump">379,687<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">104,987<span></span>
</td>
<td class="nump">48,493<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">12<span></span>
</td>
<td class="nump">19<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(1,686)<span></span>
</td>
<td class="num">(18)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">103,313<span></span>
</td>
<td class="nump">48,494<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">28,987<span></span>
</td>
<td class="nump">72,935<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">8<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(1,541)<span></span>
</td>
<td class="num">(561)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">27,454<span></span>
</td>
<td class="nump">72,374<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">462,475<span></span>
</td>
<td class="nump">45,424<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">22<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(3,761)<span></span>
</td>
<td class="num">(64)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">458,736<span></span>
</td>
<td class="nump">45,360<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">298,431<span></span>
</td>
<td class="nump">137,635<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">13<span></span>
</td>
<td class="nump">139<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(6,247)<span></span>
</td>
<td class="num">(500)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">292,197<span></span>
</td>
<td class="nump">137,274<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">72,059<span></span>
</td>
<td class="nump">134,770<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">45<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(797)<span></span>
</td>
<td class="num">(37)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">71,262<span></span>
</td>
<td class="nump">134,778<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">14,591<span></span>
</td>
<td class="nump">39,909<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2<span></span>
</td>
<td class="nump">1<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(540)<span></span>
</td>
<td class="num">(224)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">14,053<span></span>
</td>
<td class="nump">39,686<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember', window );">Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">6,040<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(76)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">5,964<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,136<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(37)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,099<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=ions_EquitySecuritiesPubliclyTradedCompaniesMember', window );">Publicly Traded Equity Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFVNIAbstract', window );"><strong>Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">15,097<span></span>
</td>
<td class="nump">11,897<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">7,145<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(7,841)<span></span>
</td>
<td class="num">(837)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">7,256<span></span>
</td>
<td class="nump">18,205<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract', window );"><strong>Available-for-sale and Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedLoss', window );">Unrealized loss on equity investment</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(10,900)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=ions_EquitySecuritiesPrivateCompaniesMember', window );">Privately Held Equity Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFVNIAbstract', window );"><strong>Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">23,115<span></span>
</td>
<td class="nump">15,615<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">17,257<span></span>
</td>
<td class="nump">16,707<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 40,372<span></span>
</td>
<td class="nump">$ 32,322<span></span>
</td>
</tr>
<tr><td colspan="3"></td></tr>
<tr><td colspan="3"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Includes investments classified as cash equivalents in our condensed consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Our equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the nine months ended&#160;September 30, 2022, we recognized a $10.9 million unrealized non-cash loss in our condensed consolidated statement of operations related to a decrease in the fair value of our investments in publicly traded companies.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at</span> cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></td>
</tr>
</table></td></tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of (1) investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of (1) amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) cost of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of (1) unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) unrealized gain on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of (1) unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Accumulated amount of unrealized gain on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Accumulated amount of unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of privately-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for under the cost method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of publicly-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for at fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26610-111562<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26626-111562<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(12))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26626-111562<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=124098289&amp;loc=d3e6676-107765<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -URI https://asc.fasb.org/extlink&amp;oid=123594786&amp;loc=SL75136599-209740<br></p></div>
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<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cost of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI). Excludes equity method investment and investment in equity security without readily determinable fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 321<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=126980263&amp;loc=SL75117546-209714<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592580738896">
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<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Investments, Investments Temporarily Impaired (Details)<br> $ in Thousands</strong></div></th>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>USD ($) </div>
<div>Investment</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(20,769)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(11,860)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (32,629)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">397<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 591,245<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">133,763<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">725,008<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(10,897)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(7,084)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (17,981)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">31<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 69,640<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">53,299<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">122,939<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(875)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(2,352)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (3,227)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">74<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 643,231<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">52,767<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">695,998<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(8,327)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(1,681)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (10,008)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">140<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 40,160<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">21,769<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">61,929<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(658)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(679)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (1,337)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember', window );">Other Municipal Debt Securities [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 994<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">4,970<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">5,964<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(12)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(64)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (76)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
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<td><strong> Balance Type:</strong></td>
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<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for more than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922890-210455<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27337-111563<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121590138&amp;loc=SL82922954-210456<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for 12 months or longer, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27337-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922890-210455<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27337-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922890-210455<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121590138&amp;loc=SL82922954-210456<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922890-210455<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27337-111563<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of investments in debt securities measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without an allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922888-210455<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in unrealized loss position without allowance for credit loss.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in unrealized loss position, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
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<body>
<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592576375504">
<tr>
<th class="tl" colspan="2" rowspan="1"><div style="width: 200px;"><strong>Fair Value Measurements (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2"><div>Sep. 30, 2022</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,701,033<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 1,248,124<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 47,628<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 50,527<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=ions_EquitySecuritiesPubliclyTradedCompaniesMember', window );">Publicly Traded Equity Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 7,256<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 18,205<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member', window );">Significant Other Observable Inputs (Level 2) [Member] | 0.125% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NotesPayableFairValueDisclosure', window );">Fair value of convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">498,700<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member', window );">Significant Other Observable Inputs (Level 2) [Member] | 0% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NotesPayableFairValueDisclosure', window );">Fair value of convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">631,800<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">231,960<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">541,199<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,940,249<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,807,528<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">728,054<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">764,059<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">23,500<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">130,767<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">120,868<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">750,933<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">182,634<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">85,315<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="nump">174,464<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member] | Cash and Cash Equivalents [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">10,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">2,300<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">5,964<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,099<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Publicly Traded Equity Securities [Member] | Other Current Assets [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">7,256<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">18,205<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">231,960<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">541,199<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">990,149<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">727,708<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">750,933<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">182,634<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Publicly Traded Equity Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">7,256<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">3,875<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">950,100<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,065,490<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">728,054<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">764,059<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">130,767<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">120,868<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">85,315<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">174,464<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">5,964<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,099<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Publicly Traded Equity Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">14,330<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Publicly Traded Equity Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 0<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 14,330<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
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<tr><td colspan="6"></td></tr>
<tr><td colspan="6"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Included in cash and cash equivalents in our condensed consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">$23.5 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">Included in short-term investments.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[4]</td>
<td style="vertical-align: top;" valign="top">$10.0 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[5]</td>
<td style="vertical-align: top;" valign="top">$2.3 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.</td>
</tr>
</table></td></tr>
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<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126976982&amp;loc=d3e19207-110258<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26610-111562<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br></p></div>
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<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of currency on hand as well as demand deposits with banks or financial institutions. Includes other kinds of accounts that have the general characteristics of demand deposits. Also includes short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
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<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=124098289&amp;loc=d3e6676-107765<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -URI https://asc.fasb.org/extlink&amp;oid=123594786&amp;loc=SL75136599-209740<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of notes payable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19,20,22)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_BalanceSheetLocationAxis=us-gaap_OtherCurrentAssetsMember</td>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592586551872">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
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<tr>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AmortizationPeriodForResearchAndDevelopmentExpenditures', window );">Amortization period for research and development expenditures under IRC Section 174</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">5 years<span></span>
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<td class="text">&#160;<span></span>
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<td class="num">$ (1,307)<span></span>
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<td class="nump">$ 3,637<span></span>
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<td class="num">$ (854)<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amortization period for research and development expenditures under Internal Revenue Code Section 174, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.7)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32672-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22663-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123586238&amp;loc=d3e38679-109324<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22658-107794<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<td>duration</td>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592576580880">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Biogen (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>USD ($) </div>
<div>Payment </div>
<div>Target</div>
</th>
<th class="th">
<div>Sep. 30, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 159,767<span></span>
</td>
<td class="nump">$ 133,093<span></span>
</td>
<td class="nump">$ 435,478<span></span>
</td>
<td class="nump">$ 370,450<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">61,647<span></span>
</td>
<td class="nump">66,572<span></span>
</td>
<td class="nump">175,092<span></span>
</td>
<td class="nump">198,726<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">87,357<span></span>
</td>
<td class="nump">48,273<span></span>
</td>
<td class="nump">212,599<span></span>
</td>
<td class="nump">115,321<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen Collaborations [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">3,400,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3,400,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">89,000<span></span>
</td>
<td class="nump">$ 84,000<span></span>
</td>
<td class="nump">259,700<span></span>
</td>
<td class="nump">$ 262,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="nump">$ 360,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 360,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 407,500<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen Collaborations [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">56.00%<span></span>
</td>
<td class="nump">63.00%<span></span>
</td>
<td class="nump">60.00%<span></span>
</td>
<td class="nump">71.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen Collaborations [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 61,600<span></span>
</td>
<td class="nump">$ 66,600<span></span>
</td>
<td class="nump">$ 175,100<span></span>
</td>
<td class="nump">$ 198,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen Collaborations [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">27,400<span></span>
</td>
<td class="nump">$ 17,400<span></span>
</td>
<td class="nump">84,600<span></span>
</td>
<td class="nump">$ 63,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember', window );">Neurology Collaborations with Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 13,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfTargetsAdvanced', window );">Number of targets advanced | Target</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfMilestonePaymentsRecognizedInFull', window );">Number of milestone payments recognized in full | Payment</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology Collaboration with Biogen [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="nump">$ 10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPotentialPayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next potential payment to be earned under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPotentialPayment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfMilestonePaymentsRecognizedInFull">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of milestone payments recognized in full during the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfMilestonePaymentsRecognizedInFull</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfTargetsAdvanced">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of targets advanced under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfTargetsAdvanced</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI https://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborations2013StrategicNeurologyAnd2012NeurologyMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
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<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Roche (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
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<div>Sep. 30, 2022 </div>
<div>USD ($) </div>
<div>Indication </div>
<div>Agreement</div>
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<th class="th">
<div>Jun. 30, 2022 </div>
<div>USD ($)</div>
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<th class="th">
<div>Sep. 30, 2021 </div>
<div>USD ($)</div>
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<div>Sep. 30, 2022 </div>
<div>USD ($) </div>
<div>Indication </div>
<div>Agreement</div>
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<div>Sep. 30, 2021 </div>
<div>USD ($)</div>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 133,093<span></span>
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<td class="nump">$ 435,478<span></span>
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<td class="nump">$ 370,450<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 87,357<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 48,273<span></span>
</td>
<td class="nump">$ 212,599<span></span>
</td>
<td class="nump">$ 115,321<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember', window );">Roche Collaborations [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfCollaborationAgreements', window );">Number of collaboration agreements | Agreement</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 283,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 283,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="nump">$ 23,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 23,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 31,600<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember', window );">Roche Collaborations [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">26.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3.00%<span></span>
</td>
<td class="nump">15.00%<span></span>
</td>
<td class="nump">3.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember', window );">Roche Collaborations [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 41,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 3,900<span></span>
</td>
<td class="nump">$ 65,400<span></span>
</td>
<td class="nump">$ 11,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember', window );">Collaboration to Develop IONIS-FB-L with Roche [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfCollaborationAgreements', window );">Number of collaboration agreements | Agreement</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfDiseaseIndications', window );">Number of disease indications | Indication</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="nump">$ 145,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 145,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="nump">279,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">279,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones', window );">Maximum amount of payments receivable for sales-related milestones</a></td>
<td class="nump">280,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 280,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">35,000<span></span>
</td>
<td class="nump">$ 13,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember', window );">Collaboration to Develop IONIS-FB-L with Roche [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPotentialMilestonePayment', window );">Next prospective milestone</a></td>
<td class="nump">$ 90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember', window );">Collaboration to Develop IONIS-FB-L with Roche [Member] | GA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfDiseaseIndications', window );">Number of disease indications | Indication</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember', window );">Collaboration to Develop IONIS-FB-L with Roche [Member] | IgAN [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfDiseaseIndications', window );">Number of disease indications | Indication</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationHuntingtonsDiseaseMember', window );">Collaboration to Develop Treatments for Huntington's Disease with Roche [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfCollaborationAgreements', window );">Number of collaboration agreements | Agreement</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for development milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for regulatory milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for sales-related milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForSalesRelatedMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPotentialMilestonePayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next potential milestone payment to be earned under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPotentialMilestonePayment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfCollaborationAgreements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of collaboration agreements with the collaboration partner.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfCollaborationAgreements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfDiseaseIndications">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of disease indications for which studies are currently being conducted under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfDiseaseIndications</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of a medicine by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI https://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_GeographicAtrophyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_GeographicAtrophyMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ImmunoglobulinANephropathyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ImmunoglobulinANephropathyMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationHuntingtonsDiseaseMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationHuntingtonsDiseaseMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
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</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>52
<FILENAME>R42.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592585692816">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Bayer (Details)<br> $ in Millions</strong></div></th>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BayerCollaborationIonisFxiMember', window );">Bayer Collaboration [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 190<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BayerCollaborationIonisFxiMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BayerCollaborationIonisFxiMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>53
<FILENAME>R43.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
							function toggleNextSibling (e) {
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<body>
<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592581766176">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Convertible Debt (Details) - USD ($)<br> $ / shares in Units, $ in Thousands, shares in Millions</strong></div></th>
<th class="th" colspan="3">1 Months Ended</th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Nov. 30, 2021</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Jun. 30, 2021</div></th>
<th class="th"><div>Sep. 30, 2022</div></th>
<th class="th"><div>Sep. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfConvertibleDebt', window );">Repurchase of convertible notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 256,963<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CallSpread', window );">Cost of call spread</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 46,900<span></span>
</td>
<td class="nump">$ 52,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">136,700<span></span>
</td>
<td class="nump">108,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">136,620<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfWarrants', window );">Proceeds from issuance of warrants</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">89,800<span></span>
</td>
<td class="nump">$ 56,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">89,752<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Loss on early retirement of debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">$ (8,627)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount of offering</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">632,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">632,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredFinanceCostsNet', window );">Unamortized debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 11,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Apr. 30,  2026<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 57.84<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread', window );">Effective conversion price per share with call spread (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 76.39<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange', window );">Percentage of principal amount used as purchase price upon occurrence of fundamental change</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 548,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredFinanceCostsNet', window );">Unamortized debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 4,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Dec. 31,  2024<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 83.28<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread', window );">Effective conversion price per share with call spread (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 123.38<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange', window );">Percentage of principal amount used as purchase price upon occurrence of fundamental change</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentRepurchasedFaceAmount', window );">Principal amount repurchased</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">247,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 247,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfConvertibleDebt', window );">Repurchase of convertible notes</a></td>
<td class="nump">$ 62,000<span></span>
</td>
<td class="nump">$ 257,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Loss on early retirement of debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 8,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CallSpread">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The net cash outflow from payments for hedge transactions and proceeds from the issuance of warrants. The call spread transaction was entered into to minimize the impact of potential economic dilution upon conversion of the 0.125% notes issued.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CallSpread</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The computed conversion price per share of the debt instrument based on the the conversion feature embedded in the debt instrument and the impact of the purchased hedges in the call spread transaction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of the principal amount of the notes to be purchased, plus accrued and unpaid interest, upon the occurrence of certain fundamental changes, as set forth in the indenture governing the convertible notes.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentConvertibleSharesSubjectToConversion">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of shares of common stock subject to conversion if the debt was converted to equity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtInstrumentConvertibleSharesSubjectToConversion</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentCarryingAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before unamortized (discount) premium and debt issuance costs, of long-term debt. Includes, but is not limited to, notes payable, bonds payable, commercial loans, mortgage loans, convertible debt, subordinated debt and other types of debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466204&amp;loc=SL6031897-161870<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(16))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentCarryingAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentConvertibleConversionPrice1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The price per share of the conversion feature embedded in the debt instrument.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 5<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466204&amp;loc=SL6031898-161870<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentConvertibleConversionPrice1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentFaceAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face (par) amount of debt instrument at time of issuance.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28551-108399<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=114775985&amp;loc=d3e28878-108400<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124429444&amp;loc=SL124452920-239629<br><br>Reference 5: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 55<br> -Paragraph 69C<br> -URI https://asc.fasb.org/extlink&amp;oid=123466577&amp;loc=SL123495737-112612<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 55<br> -Paragraph 69B<br> -URI https://asc.fasb.org/extlink&amp;oid=123466577&amp;loc=SL123495735-112612<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentFaceAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Effective interest rate for the funds borrowed under the debt agreement considering interest compounding and original issue discount or premium.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466204&amp;loc=SL6036836-161870<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28551-108399<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124429444&amp;loc=SL124452920-239629<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateEffectivePercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentMaturityDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Date when the debt instrument is scheduled to be fully repaid, in YYYY-MM-DD format.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=126976982&amp;loc=d3e19207-110258<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentMaturityDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:dateItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentRepurchasedFaceAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face (par) amount of the original debt instrument that was repurchased.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentRepurchasedFaceAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredFinanceCostsNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after accumulated amortization, of debt issuance costs. Includes, but is not limited to, legal, accounting, underwriting, printing, and registration costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1D<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495340-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28555-108399<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredFinanceCostsNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainsLossesOnExtinguishmentOfDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Difference between the fair value of payments made and the carrying amount of debt which is extinguished prior to maturity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=126972273&amp;loc=d3e12355-112629<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126972273&amp;loc=d3e12317-112629<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainsLossesOnExtinguishmentOfDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsForHedgeFinancingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for a financial contract that meets the hedge criteria as either cash flow hedge, fair value hedge or hedge of net investment in foreign operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 27<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3581-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsForHedgeFinancingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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<span style="display: none;">v3.22.2.2</span><table class="report" border="0" cellspacing="2" id="idm140592576431824">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Legal Proceedings (Details) - John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al. [Member]<br> $ in Millions</strong></div></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Jun. 03, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Aug. 05, 2021 </div>
<div>Plaintiff</div>
</th>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2022 </div>
<div>USD ($)</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LossContingencyClaimsQuantitiesAbstract', window );"><strong>Legal Procedings [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LossContingencyNumberOfPlaintiffs', window );">Number of plaintiffs | Plaintiff</a></td>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 4.8<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_LitigationCaseAxis=ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember', window );">Other Expense [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LossContingencyClaimsQuantitiesAbstract', window );"><strong>Legal Procedings [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LitigationSettlementExpense', window );">Litigation settlement expense</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount awarded to other party in judgment or settlement of litigation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of litigation expense, including but not limited to legal, forensic, accounting, and investigative fees.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of plaintiffs that have filed claims pertaining to a loss contingency.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 450<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=121557415&amp;loc=d3e14435-108349<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 450<br> -SubTopic 20<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=121557415&amp;loc=d3e14557-108349<br></p></div>
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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1.&#160; Basis of Presentation&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended&#160;September 30, 2022 and 2021 on the same basis as the audited financial statements for the year ended December 31, 2021. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2021 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#x201c;we&#x201d;, &#x201c;us&#x201d; or &#x201c;our&#x201d;).&lt;/div&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended&#160;September 30, 2022 and 2021 on the same basis as the audited financial statements for the year ended December 31, 2021. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2021 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.&lt;/div&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#x201c;we&#x201d;, &#x201c;us&#x201d; or &#x201c;our&#x201d;).&lt;/div&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2.&#160; Significant Accounting Policies&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Revenue Recognition&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Our Revenue Sources&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts within deferred revenue in our condensed consolidated balance sheet.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements&lt;/span&gt;, or ASC 808. ASC 808 does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC 606, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Revenue from Contracts with Customers&lt;/span&gt;. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We also recognize sales milestone payments and royalties we earn under our other partnerships as commercial revenue.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Research and development revenue under collaborative agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, research and development, or R&amp;amp;D, services, and manufacturing services.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;See &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note 6, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, for collaborations with substantive changes that occurred in 2022. Additionally, see &lt;/span&gt;Note 6, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/span&gt;, in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2021 for a summary of each of our material collaborative agreements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Steps to Recognize Revenue&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;1.&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Identify the contract&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We and our partner approved the contract and we are both committed to perform our obligations;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have identified our rights, our partner&#x2019;s rights and the payment terms;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We believe collectability of the consideration is probable.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;2&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;.&lt;/span&gt;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Identify the performance obligations&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Often we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;3.&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Determine the transaction price&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/or are usually based on scientific progress which is inherently uncertain. For example, in the first quarter of 2022, we earned a $10 million milestone payment from Biogen when Biogen advanced the Phase 1/2 study for ION859, an investigational antisense medicine targeting leucine rich repeat kinase 2, or LRRK2, in patients with Parkinson&#x2019;s disease. We did not consider the milestone payment probable until Biogen achieved the milestone event because advancing ION859 was contingent on Biogen advancing a Phase 1/2 study and was not within our control. We recognized the milestone payment in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;4.&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Allocate the transaction price&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Next, we allocate the transaction price to each of our performance obligations. When we have to allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated future product sales;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated royalties we may receive from future product sales;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated contractual milestone payments we may receive;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated expenses we may incur;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated income taxes; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;A discount rate.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We typically estimate the selling price of R&amp;amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;amp;D services include:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated number of internal hours we will spend performing these services;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of work we will perform;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of work that we will contract with third parties to perform; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of API we will use.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For purposes of determining the stand-alone selling price of the R&amp;amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.&lt;/div&gt;

&lt;div style="text-align: justify;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;5.&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Recognize revenue&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For R&amp;amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following are examples of when we typically recognize revenue based on the types of payments we receive.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize royalty revenue, including royalties from SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#x2019;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;amp;A, expenses in our condensed consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Reserves for TEGSEDI and WAYLIVRA commercial revenue&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our distribution agreements with Sobi, Sobi is responsible for any applicable reserves.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Prior to our distribution agreements with Sobi, w&lt;/span&gt;e recorded TEGSEDI and WAYLIVRA commercial revenue at our net sales price, or transaction price. We included in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offered within contracts between us and our customers, wholesalers, distributors, health care providers and other indirect customers. We estimated our reserves using the amounts we have earned or we could claim on the associated sales. We classified our reserves as a reduction of accounts receivable when we were not required to make a payment or as a current liability when we were required to make a payment. In certain cases, our estimates included a range of possible outcomes that were probability weighted for relevant factors such as our historical experience, contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflected our best estimates under the terms of our respective contracts. When calculating our reserves and related TEGSEDI and WAYLIVRA commercial revenue, we only recognized amounts to the extent that we considered it probable that we would not have to reverse a significant amount of the cumulative sales we previously recognized in a future period. Under our agreements with Sobi, we transferred all reserves to Sobi. See our revenue recognition policy in Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and Significant Accounting Policies&lt;/span&gt;, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2021 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales prior to our agreements with Sobi.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Research and development revenue under collaboration agreements:&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Upfront payments&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;When we enter into a collaboration agreement and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;amp;D services. For example, under our collaboration agreement with Roche to develop IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt; for the treatment of complement-mediated diseases, we received a $75 million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;amp;D services. We are amortizing the $75 million upfront payment using an input method over the estimated period of time we are providing R&amp;amp;D services.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Milestone payments&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the second quarter of 2022, we achieved a $20 million milestone payment from Roche when we advanced the Phase 2 study in patients with dry age-related macular degeneration, or AMD, under our collaboration agreement with Roche to develop IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt;. We added this payment to the transaction price and allocated it to our R&amp;amp;D services performance obligation for IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt;. We are recognizing revenue related to this milestone payment over our estimated period of performance. As a result, we recorded a cumulative catch-up adjustment of $13.8 million to increase revenue in the second quarter of 2022 for this payment. We estimate we will satisfy our performance obligation in the fourth quarter of 2023.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversely, we recognize in full those milestone payments that we earn based on our partners&#x2019; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2022, we recognized $13 million in milestone payments when Biogen advanced two targets under our neurology collaborations. We concluded that these milestone payments were not related to our R&amp;amp;D services performance obligations for these collaborations. Therefore, we recognized the milestone payments in full in the third quarter of 2022.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;License fees&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. For example, in the third quarter of 2022, we earned a $35 million license fee from Roche when Roche licensed IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt;, an investigational medicine in development to treat complement-mediated diseases.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Sublicense fees&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not have any performance obligations related to the sublicense. For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Amendments to Agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the goods and/or services are sold at a stand-alone selling price.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Multiple agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the agreements were negotiated together with a single objective;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the goods and/or services promised under the agreements are a single performance obligation.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: a new strategic neurology collaboration agreement and a stock purchase agreement. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Eplontersen Collaboration with AstraZeneca&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a result we had one performance obligation.&#160; For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#x2019;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related to commercial and medical affairs activities as reductions of our SG&amp;amp;A expense and R&amp;amp;D expense, respectively. Refer to Item 2, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Management&#x2019;s Discussion and Analysis of Financial Condition and Results of Operations&lt;/span&gt;, for further details on the financial statement impacts of our eplontersen collaboration with AstraZeneca. &lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contracts Receivable&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our contracts receivable balance represents the amounts we have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts receivable to be unconditional. We typically receive payment within &lt;/span&gt;&lt;span style="-sec-ix-hidden:Fact_cb46feec840d4d05b86df2a2af3b44c3"&gt;one quarter&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of billing our partner or customer&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of September 30, 2022, approximately 73.1 percent of our contracts receivables were from two significant customers. As of December 31, 2021, approximately 93.8 percent of our contracts receivables were from two significant customers.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unbilled SPINRAZA Royalties&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen for SPINRAZA royalties. We include these unbilled amounts in other current assets on our condensed consolidated balance sheet.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Deferred Revenue&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are often entitled to bill our customers and receive payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue on our condensed consolidated balance sheet.&lt;/span&gt; During the three months ended&#160;September 30, 2022 and 2021, we recognized $23.1 million and $21.1 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;During the &lt;/span&gt;nine months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;September 30, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we recognized $&lt;/span&gt;69.8&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;71.9&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. &lt;/span&gt;For further discussion, refer to our revenue recognition policy above.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost of Sales&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales. &lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Accrued Liabilities&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our accrued liabilities consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30, 2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Clinical development expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;103,635&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,730&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In-licensing expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,130&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,044&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,188&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,471&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other miscellaneous expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13,049&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total accrued liabilities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;128,002&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;88,560&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Estimated Liability for Clinical Development Expenses&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly basis, we estimate our liability for preclinical and clinical development expenses we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these expenses. These expenses primarily relate to third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon settlement, these expenses may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cash, Cash Equivalents and Investments&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#x201c;available-for-sale&#x201d; and carry them at fair market value based upon prices on the last day of the fiscal period for identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our condensed consolidated statement of operations. We use the specific identification method to determine the cost of securities sold.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At September 30, 2022, we held equity investments in three publicly held companies and eight privately held companies.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our condensed consolidated statement of operations. We account for our equity investments in publicly held companies based on observable inputs such as quoted prices in active markets for identical assets. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. We recorded an immaterial amount of fair value adjustments related to our equity investments for the three and nine months ended&#160;September 30, 2022 and 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Inventory Valuation&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or net realizable value under the first-in, first-out method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials, they have alternative future uses, which we refer to as clinical raw materials. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency. Our raw materials - commercial inventory includes API for our commercial medicines. We capitalize material, labor and overhead costs as part of our raw materials - commercial inventory.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our inventory consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30, 2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- clinical&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,507&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- commercial&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,139&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total raw materials&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,617&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,740&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Finished goods&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;288&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;390&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventory&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,645&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,806&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determine if an arrangement contains a lease at inception of the arrangement. As of September 30, 2022, we only had operating leases. We recognize a right-of-use operating lease asset and associated short- and long-term operating lease liability on our condensed consolidated balance sheet for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we will pay over the lease term. We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal options if we concluded we were reasonably certain that we will exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease term.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commenced in January 2022 when the office space was ready for our tenant&#x2019;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending in November 2028 with no option to extend the sublease. Under the sublease agreement we provided a seven-month free rent period, which commenced in January 2022. We will receive lease payments over the sublease term totaling $9.6 million. We are recognizing sublease payments as other income on a straight-line, gross basis over the term of our sublease.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility in Oceanside, California. The lessor will develop and construct a building composed of manufacturing space, office space, research and development space and warehouse space. We will design and construct tenant improvements to customize the facility&#x2019;s interior space. We will lease the facility for an initial term of &lt;span style="-sec-ix-hidden:Fact_f55efb1442234cfa8ea3fb7d8884b511"&gt;20 years and 3 months&lt;/span&gt; with options to extend the lease for two additional terms of 10 years each. The lease will commence when the lessor's construction is complete and we are able to occupy the facility.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2022, we concurrently entered into two purchase and sale agreements with a real estate investor. Under the agreements, we sold and leased back the facilities at our headquarters location in Carlsbad, California and will sell, subject to meeting certain closing conditions, two lots of undeveloped land adjacent to our headquarters. We sold the facilities at our headquarters for a total purchase price of $263.4 million and we expect to receive total proceeds of $33.0 million upon the close of the sale of the two lots. We used a portion of the sale proceeds to extinguish our mortgage debt on our headquarters facilities of $51.3 million. The initial lease term for our headquarters facilities is 15 years with options to extend the lease for two additional terms of five years each. In connection with the sale of our two undeveloped lots, we will enter into a build-to-suit lease agreement with the same real estate investor who will build a new R&amp;amp;D facility for us on those lots. Once this new facility is completed, our lease will commence.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Research, Development and Patent Expenses&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our condensed consolidated balance sheet and we expense them as the services are provided.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the U.S. Patent and Trademark Office, or foreign equivalent, issues the patent. &lt;/span&gt;We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income Taxes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes. Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the provision for income taxes in the period in which we make such determination.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Long-lived Assets&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluate long-lived assets, which include property, plant and equipment, right-of-use assets and patent costs, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Use of Estimates&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the &lt;/span&gt;U.S. that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic and Diluted Net Loss Per Share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Basic net loss per share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our basic net loss per share for the three and nine months ended&#160;September 30, 2022 and 2021 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Our basic net loss per share for the three months ended September 30, 2022 and 2021 were $0.33 and $0.58, respectively. Our basic net loss per share for the nine months ended&#160;September 30, 2022 and 2021 were $1.53 and $1.80, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Diluted net loss per share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three and nine months ended&#160;September 30, 2022 and 2021, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent convertible senior notes, or 0% Notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Note hedges related to the 0% Notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent convertible senior notes, or 0.125% Notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Note hedges related to the 0.125% Notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dilutive stock options;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested restricted stock units, or RSUs;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested performance restricted stock units, or PRSUs; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Employee Stock Purchase Plan, or ESPP.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three and nine months ended&#160;September 30, 2021, common stock that we could have issued from our 1 percent convertible senior notes, or 1% Notes, would also have had an anti-dilutive effect on net loss per share.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additionally as of September 30, 2022, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Convertible Debt&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Derivatives and Hedging&lt;/span&gt;, or ASC 815, and our convertible debt instruments were not issued at a substantial premium. We record the entire debt issuance costs as a contra-liability in our condensed consolidated balance sheet at issuance and we amortize them over the contractual term using an updated effective interest rate. As such, the ending balances for our 0% and 0.125% Notes represent the principal balance of each convertible debt instrument less debt issuance costs. We amortize debt issuance costs for our 0% and 0.125% Notes over the respective contractual term using an effective interest rate of 0.5 percent for each note. Refer to Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Convertible Debt&lt;/span&gt;, for further details on our convertible debt instruments.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with the issuance of our 0% Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not meet the definition of a liability using the guidance contained in ASC Topic 480, therefore we account for the note hedges and warrants using the Derivatives and Hedging &#x2013; Contracts in Entity&#x2019;s Own Equity accounting guidance contained in ASC 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified in shareholders&#x2019; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our condensed consolidated balance sheet. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Segment Information&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We operate as a &lt;span style="-sec-ix-hidden:Fact_ba6a4e8bb35940dbbf919d263b57d70e"&gt;single&lt;/span&gt; segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock-based Compensation Expense&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;On the grant date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the awards, and actual and projected employee stock option exercise behaviors.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or 2020 Plan. As a result, all employees are now under an Ionis stock plan and subject to the same Black-Scholes assumptions.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the nine months ended&#160;September 30, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Employee Stock Options:&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life*&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.3 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.9 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;*&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the nine months ended&#160;September 30, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns. &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis Board of Director Stock Options:&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.4 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.3 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;ESPP:&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;RSU&#x2019;s:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. The RSUs we granted after June 2020 to our board of directors fully vest after one year. The weighted-average grant date fair value of RSUs granted to employees and our board of directors for the nine months ended&#160;September 30, 2022 were $34.88 and $38.06 per share, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;PRSU&#x2019;s:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added PRSU awards to the compensation for our other Section 16 officers. Under the terms of the grants, &lt;span style="-sec-ix-hidden:Fact_3ea144f70898401099a1731ad0c7e39f"&gt;&lt;span style="-sec-ix-hidden:Fact_b531c97d5a394e3f8a5454ecd82ddb93"&gt;&lt;span style="-sec-ix-hidden:Fact_b2b6dbe875764e78b9cce0b8464216dd"&gt;one third&lt;/span&gt;&lt;/span&gt;&lt;/span&gt; of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero percentto 150 percent of the target number depending on our relative TSR.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to our Section 16 officers for the nine months ended&#160;September 30, 2022 and 2021 were $42.28 and $77.17 per share, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes stock-based compensation expense for the three and nine months ended&#160;September 30, 2022 and 2021 (in thousands).&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"/&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cost of sales&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;163&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;111&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;376&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research, development and patent expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,733&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,332&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,979&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,941&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,094&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,884&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,147&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total stock-based compensation expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30,537&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,575&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;98,419&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of September 30, 2022, total unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $50.9 million, $53.0 million and $3.4 million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures. We expect to recognize the cost of stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.2 years, 1.4 years and 1.1 years, respectively. Our stock-based compensation expense related to equity awards decreased in the three and nine months ended September 30, 2022 compared to the same periods in 2021 due to decreased headcount of longer-tenured employees as a result of restructuring our commercial operations for TEGSEDI and WAYLIVRA.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Recently Adopted Accounting Standards&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In June 2022, the Financial Accounting Standards Board, or FASB, issued clarifying guidance on fair value measurement of equity securities subject to contractual trading restrictions. The guidance clarifies that contractual trading restrictions are not considered part of the unit of account of equity securities and therefore, are not considered when measuring the fair value of equity securities. This update is effective for interim and annual periods beginning January 1, 2024 on a prospective basis. Early adoption of this guidance is permitted at an interim or annual period. We early adopted this new guidance in the third quarter of 2022. This guidance did not have an impact on our condensed consolidated financial statements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not expect any other recently issued accounting standards to have a material impact to our financial results.&lt;/div&gt;
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    <us-gaap:RevenueFromContractWithCustomerPolicyTextBlock
      contextRef="c20220101to20220930"
      id="Text_23dcd0c53d73416a92d74f38fe21501a">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Revenue Recognition&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Our Revenue Sources&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts within deferred revenue in our condensed consolidated balance sheet.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements&lt;/span&gt;, or ASC 808. ASC 808 does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC 606, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Revenue from Contracts with Customers&lt;/span&gt;. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We also recognize sales milestone payments and royalties we earn under our other partnerships as commercial revenue.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Research and development revenue under collaborative agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, research and development, or R&amp;amp;D, services, and manufacturing services.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;See &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note 6, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, for collaborations with substantive changes that occurred in 2022. Additionally, see &lt;/span&gt;Note 6, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/span&gt;, in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2021 for a summary of each of our material collaborative agreements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Steps to Recognize Revenue&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;1.&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Identify the contract&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We and our partner approved the contract and we are both committed to perform our obligations;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have identified our rights, our partner&#x2019;s rights and the payment terms;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We believe collectability of the consideration is probable.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;2&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;.&lt;/span&gt;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Identify the performance obligations&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Often we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;3.&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Determine the transaction price&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/or are usually based on scientific progress which is inherently uncertain. For example, in the first quarter of 2022, we earned a $10 million milestone payment from Biogen when Biogen advanced the Phase 1/2 study for ION859, an investigational antisense medicine targeting leucine rich repeat kinase 2, or LRRK2, in patients with Parkinson&#x2019;s disease. We did not consider the milestone payment probable until Biogen achieved the milestone event because advancing ION859 was contingent on Biogen advancing a Phase 1/2 study and was not within our control. We recognized the milestone payment in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;4.&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Allocate the transaction price&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Next, we allocate the transaction price to each of our performance obligations. When we have to allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated future product sales;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated royalties we may receive from future product sales;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated contractual milestone payments we may receive;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated expenses we may incur;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated income taxes; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;A discount rate.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We typically estimate the selling price of R&amp;amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;amp;D services include:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated number of internal hours we will spend performing these services;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of work we will perform;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of work that we will contract with third parties to perform; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of API we will use.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For purposes of determining the stand-alone selling price of the R&amp;amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.&lt;/div&gt;

&lt;div style="text-align: justify;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;5.&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Recognize revenue&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For R&amp;amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following are examples of when we typically recognize revenue based on the types of payments we receive.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize royalty revenue, including royalties from SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#x2019;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;amp;A, expenses in our condensed consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Reserves for TEGSEDI and WAYLIVRA commercial revenue&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our distribution agreements with Sobi, Sobi is responsible for any applicable reserves.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Prior to our distribution agreements with Sobi, w&lt;/span&gt;e recorded TEGSEDI and WAYLIVRA commercial revenue at our net sales price, or transaction price. We included in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offered within contracts between us and our customers, wholesalers, distributors, health care providers and other indirect customers. We estimated our reserves using the amounts we have earned or we could claim on the associated sales. We classified our reserves as a reduction of accounts receivable when we were not required to make a payment or as a current liability when we were required to make a payment. In certain cases, our estimates included a range of possible outcomes that were probability weighted for relevant factors such as our historical experience, contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflected our best estimates under the terms of our respective contracts. When calculating our reserves and related TEGSEDI and WAYLIVRA commercial revenue, we only recognized amounts to the extent that we considered it probable that we would not have to reverse a significant amount of the cumulative sales we previously recognized in a future period. Under our agreements with Sobi, we transferred all reserves to Sobi. See our revenue recognition policy in Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and Significant Accounting Policies&lt;/span&gt;, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2021 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales prior to our agreements with Sobi.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Research and development revenue under collaboration agreements:&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Upfront payments&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;When we enter into a collaboration agreement and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;amp;D services. For example, under our collaboration agreement with Roche to develop IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt; for the treatment of complement-mediated diseases, we received a $75 million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;amp;D services. We are amortizing the $75 million upfront payment using an input method over the estimated period of time we are providing R&amp;amp;D services.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Milestone payments&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the second quarter of 2022, we achieved a $20 million milestone payment from Roche when we advanced the Phase 2 study in patients with dry age-related macular degeneration, or AMD, under our collaboration agreement with Roche to develop IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt;. We added this payment to the transaction price and allocated it to our R&amp;amp;D services performance obligation for IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt;. We are recognizing revenue related to this milestone payment over our estimated period of performance. As a result, we recorded a cumulative catch-up adjustment of $13.8 million to increase revenue in the second quarter of 2022 for this payment. We estimate we will satisfy our performance obligation in the fourth quarter of 2023.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversely, we recognize in full those milestone payments that we earn based on our partners&#x2019; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2022, we recognized $13 million in milestone payments when Biogen advanced two targets under our neurology collaborations. We concluded that these milestone payments were not related to our R&amp;amp;D services performance obligations for these collaborations. Therefore, we recognized the milestone payments in full in the third quarter of 2022.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;License fees&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. For example, in the third quarter of 2022, we earned a $35 million license fee from Roche when Roche licensed IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt;, an investigational medicine in development to treat complement-mediated diseases.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Sublicense fees&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not have any performance obligations related to the sublicense. For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Amendments to Agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the goods and/or services are sold at a stand-alone selling price.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Multiple agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the agreements were negotiated together with a single objective;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the goods and/or services promised under the agreements are a single performance obligation.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: a new strategic neurology collaboration agreement and a stock purchase agreement. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Eplontersen Collaboration with AstraZeneca&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a result we had one performance obligation.&#160; For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#x2019;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related to commercial and medical affairs activities as reductions of our SG&amp;amp;A expense and R&amp;amp;D expense, respectively. Refer to Item 2, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Management&#x2019;s Discussion and Analysis of Financial Condition and Results of Operations&lt;/span&gt;, for further details on the financial statement impacts of our eplontersen collaboration with AstraZeneca. &lt;/div&gt;
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      contextRef="c20201001to20201231_TypeOfArrangementAxis_AlnylamCollaborationMember"
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      contextRef="c20180401to20180630_MajorCustomersAxis_BiogenIncMember"
      decimals="INF"
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      contextRef="c20210101to20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
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      id="Fact_53da6e65fb0741c483420c0238104ade"
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      id="Fact_b27e54c14e90416580647f971d492180"
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      contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="INF"
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    <ions:RevenueFromContractWithCustomerTransactionPrice
      contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="-6"
      id="Fact_387a94400e2542adb3feef5e16cbd22c"
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    <ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner
      contextRef="c20220101to20220930_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="2"
      id="Fact_3165c6664dcc46f6bd3fb9a729593495"
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    <us-gaap:ReceivablesPolicyTextBlock
      contextRef="c20220101to20220930"
      id="Text_65525657713c48478f6f26b531ff73b7">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contracts Receivable&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our contracts receivable balance represents the amounts we have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts receivable to be unconditional. We typically receive payment within &lt;/span&gt;&lt;span style="-sec-ix-hidden:Fact_cb46feec840d4d05b86df2a2af3b44c3"&gt;one quarter&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of billing our partner or customer&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of September 30, 2022, approximately 73.1 percent of our contracts receivables were from two significant customers. As of December 31, 2021, approximately 93.8 percent of our contracts receivables were from two significant customers.&lt;/div&gt;
</us-gaap:ReceivablesPolicyTextBlock>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20220101to20220930_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember"
      decimals="3"
      id="Fact_ddb9c9779caa4c7ba7a8628627b81f91"
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    <ions:NumberOfSignificantCustomers
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    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember"
      decimals="3"
      id="Fact_2797753f496a4c3a9e250ecbc9db8bec"
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    <ions:NumberOfSignificantCustomers
      contextRef="c20210101to20211231"
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    <us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy
      contextRef="c20220101to20220930"
      id="Text_6f3107eba95140ffb1c98fd3296491db">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unbilled SPINRAZA Royalties&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen for SPINRAZA royalties. We include these unbilled amounts in other current assets on our condensed consolidated balance sheet.&lt;/div&gt;
</us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy>
    <us-gaap:RevenueRecognitionPolicyTextBlock
      contextRef="c20220101to20220930"
      id="Text_1fffd2b34a31436fa2700206d4f2a54a">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Deferred Revenue&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are often entitled to bill our customers and receive payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue on our condensed consolidated balance sheet.&lt;/span&gt; During the three months ended&#160;September 30, 2022 and 2021, we recognized $23.1 million and $21.1 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;During the &lt;/span&gt;nine months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;September 30, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we recognized $&lt;/span&gt;69.8&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;71.9&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. &lt;/span&gt;For further discussion, refer to our revenue recognition policy above.&lt;/div&gt;
</us-gaap:RevenueRecognitionPolicyTextBlock>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
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      decimals="-5"
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    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20210701to20210930"
      decimals="-5"
      id="Fact_8467a8264e824b68904b44a564361380"
      unitRef="U002">21100000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20220101to20220930"
      decimals="-5"
      id="Fact_5f0eaf8c9d8c408da05cc1e442f052d3"
      unitRef="U002">69800000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20210101to20210930"
      decimals="-5"
      id="Fact_51a5fbfebaa247199fd1c1ee337783af"
      unitRef="U002">71900000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:CostOfSalesPolicyTextBlock
      contextRef="c20220101to20220930"
      id="Text_a7157f5414bc403797c3de4182f78f4f">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost of Sales&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales. &lt;/div&gt;
</us-gaap:CostOfSalesPolicyTextBlock>
    <ions:AccruedClinicalDevelopmentExpenses
      contextRef="c20220930"
      decimals="-3"
      id="Fact_9fa65e9eb4874e529d2b5a8558dbeefc"
      unitRef="U002">103635000</ions:AccruedClinicalDevelopmentExpenses>
    <ions:AccruedClinicalDevelopmentExpenses
      contextRef="c20211231"
      decimals="-3"
      id="Fact_e1554d35bd0e4c82aabac0d765ba6ddc"
      unitRef="U002">65730000</ions:AccruedClinicalDevelopmentExpenses>
    <ions:AccruedInLicensingFeesCurrent
      contextRef="c20220930"
      decimals="-3"
      id="Fact_c222f622055145968e8cd08ff3a569bd"
      unitRef="U002">7130000</ions:AccruedInLicensingFeesCurrent>
    <ions:AccruedInLicensingFeesCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_7076c86dd1604e5a826b9716b8c0ca6e"
      unitRef="U002">8044000</ions:AccruedInLicensingFeesCurrent>
    <ions:AccruedCommercialExpensesCurrent
      contextRef="c20220930"
      decimals="-3"
      id="Fact_74d1a19cf230440593ea60ac85e2acd3"
      unitRef="U002">4188000</ions:AccruedCommercialExpensesCurrent>
    <ions:AccruedCommercialExpensesCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_0c409149156e4e1bb3090f026e0406df"
      unitRef="U002">2471000</ions:AccruedCommercialExpensesCurrent>
    <us-gaap:OtherAccruedLiabilitiesCurrent
      contextRef="c20220930"
      decimals="-3"
      id="Fact_9ed0b35c739e48bbb51027c4ea2073ae"
      unitRef="U002">13049000</us-gaap:OtherAccruedLiabilitiesCurrent>
    <us-gaap:OtherAccruedLiabilitiesCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_b95beacb8e88464e9674b3d0a46cdaf4"
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    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20220930"
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      id="Fact_eda2e67f42534d11b5f9b63e05969ad1"
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    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20211231"
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      id="Fact_e41fd559b7f64fab9ce5f7f42569b6db"
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    <us-gaap:ResearchDevelopmentAndComputerSoftwarePolicyTextBlock
      contextRef="c20220101to20220930"
      id="Text_2310d57ea581427894838e0c7a1da3d2">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Estimated Liability for Clinical Development Expenses&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly basis, we estimate our liability for preclinical and clinical development expenses we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these expenses. These expenses primarily relate to third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon settlement, these expenses may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.&lt;/div&gt;
</us-gaap:ResearchDevelopmentAndComputerSoftwarePolicyTextBlock>
    <us-gaap:InvestmentPolicyTextBlock
      contextRef="c20220101to20220930"
      id="Text_2be3f3248a3e4b9897806424f39c50c5">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cash, Cash Equivalents and Investments&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#x201c;available-for-sale&#x201d; and carry them at fair market value based upon prices on the last day of the fiscal period for identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our condensed consolidated statement of operations. We use the specific identification method to determine the cost of securities sold.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At September 30, 2022, we held equity investments in three publicly held companies and eight privately held companies.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our condensed consolidated statement of operations. We account for our equity investments in publicly held companies based on observable inputs such as quoted prices in active markets for identical assets. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. We recorded an immaterial amount of fair value adjustments related to our equity investments for the three and nine months ended&#160;September 30, 2022 and 2021.&lt;/div&gt;
</us-gaap:InvestmentPolicyTextBlock>
    <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20220930"
      decimals="INF"
      id="Fact_8037e90f29fb43ae9797ff009a688387"
      unitRef="U010">3</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20220930"
      decimals="INF"
      id="Fact_e003aeab75174162b833cf14b3a44106"
      unitRef="U010">8</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <us-gaap:InventoryPolicyTextBlock
      contextRef="c20220101to20220930"
      id="Text_7383a8eea0944a5fa271be67a4f6a1f6">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Inventory Valuation&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or net realizable value under the first-in, first-out method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials, they have alternative future uses, which we refer to as clinical raw materials. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency. Our raw materials - commercial inventory includes API for our commercial medicines. We capitalize material, labor and overhead costs as part of our raw materials - commercial inventory.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our inventory consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30, 2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- clinical&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,507&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- commercial&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,139&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total raw materials&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,617&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,740&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Finished goods&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;288&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;390&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventory&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,645&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,806&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:InventoryPolicyTextBlock>
    <us-gaap:ScheduleOfInventoryCurrentTableTextBlock
      contextRef="c20220101to20220930"
      id="Text_36cd1b45dfff4b728da90ffcc303bb51">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our inventory consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30, 2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- clinical&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,507&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- commercial&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,139&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total raw materials&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,617&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,740&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Finished goods&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;288&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;390&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventory&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,645&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,806&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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      contextRef="c20211231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
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      contextRef="c20220930_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
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      id="Fact_4a8280762bb1470eace824e402d6b623"
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      contextRef="c20211231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
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      id="Fact_e3f1efde1cdb414796dec720e17eac54"
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      id="Fact_182d548d120f4e1daae74044c3e1bbe5"
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      contextRef="c20211231"
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      id="Fact_70a3a016ecb849cd9021230823cf224d"
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      contextRef="c20220930"
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    <us-gaap:InventoryNet
      contextRef="c20211231"
      decimals="-3"
      id="Fact_3e4c02edf53745679ae7e698216e7837"
      unitRef="U002">24806000</us-gaap:InventoryNet>
    <us-gaap:LesseeLeasesPolicyTextBlock
      contextRef="c20220101to20220930"
      id="Text_1373b62c6b744d15afe135d26a69448b">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determine if an arrangement contains a lease at inception of the arrangement. As of September 30, 2022, we only had operating leases. We recognize a right-of-use operating lease asset and associated short- and long-term operating lease liability on our condensed consolidated balance sheet for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we will pay over the lease term. We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal options if we concluded we were reasonably certain that we will exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease term.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commenced in January 2022 when the office space was ready for our tenant&#x2019;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending in November 2028 with no option to extend the sublease. Under the sublease agreement we provided a seven-month free rent period, which commenced in January 2022. We will receive lease payments over the sublease term totaling $9.6 million. We are recognizing sublease payments as other income on a straight-line, gross basis over the term of our sublease.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility in Oceanside, California. The lessor will develop and construct a building composed of manufacturing space, office space, research and development space and warehouse space. We will design and construct tenant improvements to customize the facility&#x2019;s interior space. We will lease the facility for an initial term of &lt;span style="-sec-ix-hidden:Fact_f55efb1442234cfa8ea3fb7d8884b511"&gt;20 years and 3 months&lt;/span&gt; with options to extend the lease for two additional terms of 10 years each. The lease will commence when the lessor's construction is complete and we are able to occupy the facility.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2022, we concurrently entered into two purchase and sale agreements with a real estate investor. Under the agreements, we sold and leased back the facilities at our headquarters location in Carlsbad, California and will sell, subject to meeting certain closing conditions, two lots of undeveloped land adjacent to our headquarters. We sold the facilities at our headquarters for a total purchase price of $263.4 million and we expect to receive total proceeds of $33.0 million upon the close of the sale of the two lots. We used a portion of the sale proceeds to extinguish our mortgage debt on our headquarters facilities of $51.3 million. The initial lease term for our headquarters facilities is 15 years with options to extend the lease for two additional terms of five years each. In connection with the sale of our two undeveloped lots, we will enter into a build-to-suit lease agreement with the same real estate investor who will build a new R&amp;amp;D facility for us on those lots. Once this new facility is completed, our lease will commence.&lt;/div&gt;
</us-gaap:LesseeLeasesPolicyTextBlock>
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      contextRef="c20220101to20220930_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceInBostonMassachusettsMember"
      id="Fact_47d0951dc5cf46abb2ab61b44a977bad">P7M</ions:LessorOperatingLeaseFreeRentPeriod>
    <us-gaap:LessorOperatingLeasePaymentsToBeReceived
      contextRef="c20220930_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceInBostonMassachusettsMember"
      decimals="-5"
      id="Fact_6e9e11d907a042dcbbbf9300319016c9"
      unitRef="U002">9600000</us-gaap:LessorOperatingLeasePaymentsToBeReceived>
    <ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease
      contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember"
      decimals="INF"
      id="Fact_760c2b88dc0d481e88f2d0e0c8d19af9"
      unitRef="U012">2</ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease>
    <us-gaap:LesseeOperatingLeaseRenewalTerm
      contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember"
      id="Fact_f6b3b6f9036a4d40a51e0a3f01a6c666">P10Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <ions:NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor
      contextRef="c20221001to20221031_SubsequentEventTypeAxis_SubsequentEventMember"
      decimals="INF"
      id="Fact_3a09e1ebe9164652832dfa06144761b6"
      unitRef="U006">2</ions:NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor>
    <ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement
      contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_LandMember_SubsequentEventTypeAxis_SubsequentEventMember"
      decimals="INF"
      id="Fact_fe0b2942ef0a4776b1bcf49ba82fcb2d"
      unitRef="U011">2</ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement>
    <us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment
      contextRef="c20221001to20221031_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember"
      decimals="-5"
      id="Fact_8281e5fe1022475983c06c0c19ae0e83"
      unitRef="U002">263400000</us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment>
    <us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment
      contextRef="c20221001to20221031_PropertyPlantAndEquipmentByTypeAxis_LandMember_StatementScenarioAxis_ScenarioForecastMember"
      decimals="-5"
      id="Fact_b72d83b519a34120a79d42b97f4bb816"
      unitRef="U002">33000000</us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment>
    <ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement
      contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_LandMember_SubsequentEventTypeAxis_SubsequentEventMember"
      decimals="INF"
      id="Fact_2d9295561e1746c093f8cdc68e0c9622"
      unitRef="U011">2</ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement>
    <us-gaap:RepaymentsOfSecuredDebt
      contextRef="c20221001to20221031_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember"
      decimals="-5"
      id="Fact_ef1168c278694b4490a5b679d4b1070c"
      unitRef="U002">51300000</us-gaap:RepaymentsOfSecuredDebt>
    <us-gaap:LesseeOperatingLeaseTermOfContract
      contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember"
      id="Fact_39a9279e3c6d4f3fbe9afec67e73b36a">P15Y</us-gaap:LesseeOperatingLeaseTermOfContract>
    <ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease
      contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember"
      decimals="INF"
      id="Fact_6c173c46df574b918c15a7694914e33d"
      unitRef="U012">2</ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease>
    <us-gaap:LesseeOperatingLeaseRenewalTerm
      contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember_SubsequentEventTypeAxis_SubsequentEventMember"
      id="Fact_de4bb5146b8c49379bf250eefecd6af9">P5Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement
      contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_LandMember_SubsequentEventTypeAxis_SubsequentEventMember"
      decimals="INF"
      id="Fact_0feae749ec5e4b4bbcb200fe0a289143"
      unitRef="U011">2</ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement>
    <us-gaap:ResearchAndDevelopmentExpensePolicy
      contextRef="c20220101to20220930"
      id="Text_d2e79a616c5149af971d3c0c1c8a1bfb">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our condensed consolidated balance sheet and we expense them as the services are provided.&lt;/div&gt;
</us-gaap:ResearchAndDevelopmentExpensePolicy>
    <us-gaap:IntangibleAssetsFiniteLivedPolicy
      contextRef="c20220101to20220930"
      id="Text_eae0e633d40249c1b8d1ca3267edd5ca">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the U.S. Patent and Trademark Office, or foreign equivalent, issues the patent. &lt;/span&gt;We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;
</us-gaap:IntangibleAssetsFiniteLivedPolicy>
    <us-gaap:IncomeTaxPolicyTextBlock
      contextRef="c20220101to20220930"
      id="Text_f07117ba6b154c219bc9ea7670cbc326">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income Taxes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes. Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the provision for income taxes in the period in which we make such determination.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.&lt;/div&gt;
</us-gaap:IncomeTaxPolicyTextBlock>
    <us-gaap:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock
      contextRef="c20220101to20220930"
      id="Text_f326f7d8eff14d82bfdd56e71f4064a7">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Long-lived Assets&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluate long-lived assets, which include property, plant and equipment, right-of-use assets and patent costs, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.&lt;/div&gt;
</us-gaap:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock>
    <us-gaap:UseOfEstimates
      contextRef="c20220101to20220930"
      id="Text_1b675f2ad8574bcb81c03f729eba4aa0">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Use of Estimates&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the &lt;/span&gt;U.S. that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.&lt;/div&gt;
</us-gaap:UseOfEstimates>
    <us-gaap:EarningsPerSharePolicyTextBlock
      contextRef="c20220101to20220930"
      id="Text_d8ae7016e11e44938c278329c28c5334">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic and Diluted Net Loss Per Share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Basic net loss per share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our basic net loss per share for the three and nine months ended&#160;September 30, 2022 and 2021 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Our basic net loss per share for the three months ended September 30, 2022 and 2021 were $0.33 and $0.58, respectively. Our basic net loss per share for the nine months ended&#160;September 30, 2022 and 2021 were $1.53 and $1.80, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Diluted net loss per share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three and nine months ended&#160;September 30, 2022 and 2021, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent convertible senior notes, or 0% Notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Note hedges related to the 0% Notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent convertible senior notes, or 0.125% Notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Note hedges related to the 0.125% Notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dilutive stock options;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested restricted stock units, or RSUs;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested performance restricted stock units, or PRSUs; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Employee Stock Purchase Plan, or ESPP.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three and nine months ended&#160;September 30, 2021, common stock that we could have issued from our 1 percent convertible senior notes, or 1% Notes, would also have had an anti-dilutive effect on net loss per share.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additionally as of September 30, 2022, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.&lt;/div&gt;
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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    <us-gaap:DebtPolicyTextBlock
      contextRef="c20220101to20220930"
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Convertible Debt&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Derivatives and Hedging&lt;/span&gt;, or ASC 815, and our convertible debt instruments were not issued at a substantial premium. We record the entire debt issuance costs as a contra-liability in our condensed consolidated balance sheet at issuance and we amortize them over the contractual term using an updated effective interest rate. As such, the ending balances for our 0% and 0.125% Notes represent the principal balance of each convertible debt instrument less debt issuance costs. We amortize debt issuance costs for our 0% and 0.125% Notes over the respective contractual term using an effective interest rate of 0.5 percent for each note. Refer to Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Convertible Debt&lt;/span&gt;, for further details on our convertible debt instruments.&lt;/div&gt;
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    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with the issuance of our 0% Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not meet the definition of a liability using the guidance contained in ASC Topic 480, therefore we account for the note hedges and warrants using the Derivatives and Hedging &#x2013; Contracts in Entity&#x2019;s Own Equity accounting guidance contained in ASC 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified in shareholders&#x2019; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our condensed consolidated balance sheet. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Segment Information&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We operate as a &lt;span style="-sec-ix-hidden:Fact_ba6a4e8bb35940dbbf919d263b57d70e"&gt;single&lt;/span&gt; segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment.&lt;/div&gt;
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    <us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy
      contextRef="c20220101to20220930"
      id="Text_fabff55575924204ab4d0d1a53d5fb8f">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock-based Compensation Expense&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;On the grant date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the awards, and actual and projected employee stock option exercise behaviors.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or 2020 Plan. As a result, all employees are now under an Ionis stock plan and subject to the same Black-Scholes assumptions.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the nine months ended&#160;September 30, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Employee Stock Options:&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life*&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.3 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.9 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;*&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the nine months ended&#160;September 30, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns. &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis Board of Director Stock Options:&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.4 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.3 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;ESPP:&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;RSU&#x2019;s:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. The RSUs we granted after June 2020 to our board of directors fully vest after one year. The weighted-average grant date fair value of RSUs granted to employees and our board of directors for the nine months ended&#160;September 30, 2022 were $34.88 and $38.06 per share, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;PRSU&#x2019;s:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added PRSU awards to the compensation for our other Section 16 officers. Under the terms of the grants, &lt;span style="-sec-ix-hidden:Fact_3ea144f70898401099a1731ad0c7e39f"&gt;&lt;span style="-sec-ix-hidden:Fact_b531c97d5a394e3f8a5454ecd82ddb93"&gt;&lt;span style="-sec-ix-hidden:Fact_b2b6dbe875764e78b9cce0b8464216dd"&gt;one third&lt;/span&gt;&lt;/span&gt;&lt;/span&gt; of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero percentto 150 percent of the target number depending on our relative TSR.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to our Section 16 officers for the nine months ended&#160;September 30, 2022 and 2021 were $42.28 and $77.17 per share, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes stock-based compensation expense for the three and nine months ended&#160;September 30, 2022 and 2021 (in thousands).&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"/&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cost of sales&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;163&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;111&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;376&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research, development and patent expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,733&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,332&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,979&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,941&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,094&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,884&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,147&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total stock-based compensation expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30,537&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,575&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;98,419&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of September 30, 2022, total unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $50.9 million, $53.0 million and $3.4 million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures. We expect to recognize the cost of stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.2 years, 1.4 years and 1.1 years, respectively. Our stock-based compensation expense related to equity awards decreased in the three and nine months ended September 30, 2022 compared to the same periods in 2021 due to decreased headcount of longer-tenured employees as a result of restructuring our commercial operations for TEGSEDI and WAYLIVRA.&lt;/div&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Employee Stock Options:&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life*&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.3 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.9 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;*&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the nine months ended&#160;September 30, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns. &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis Board of Director Stock Options:&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;ESPP:&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42.4&lt;/div&gt;&lt;/td&gt;
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  &lt;tr&gt;
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    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes stock-based compensation expense for the three and nine months ended&#160;September 30, 2022 and 2021 (in thousands).&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"/&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cost of sales&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;163&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;111&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;376&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research, development and patent expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,733&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,332&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,979&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,941&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,094&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,884&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,147&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total stock-based compensation expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30,537&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,575&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;98,419&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Recently Adopted Accounting Standards&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In June 2022, the Financial Accounting Standards Board, or FASB, issued clarifying guidance on fair value measurement of equity securities subject to contractual trading restrictions. The guidance clarifies that contractual trading restrictions are not considered part of the unit of account of equity securities and therefore, are not considered when measuring the fair value of equity securities. This update is effective for interim and annual periods beginning January 1, 2024 on a prospective basis. Early adoption of this guidance is permitted at an interim or annual period. We early adopted this new guidance in the third quarter of 2022. This guidance did not have an impact on our condensed consolidated financial statements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not expect any other recently issued accounting standards to have a material impact to our financial results.&lt;/div&gt;
</us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock>
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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;3.&#160; Investments&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2022:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;One year&lt;/span&gt; or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;66&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After &lt;span style="text-indent: 0pt;"&gt;one year&lt;/span&gt; but within &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt; but within &lt;span style="text-indent: 0pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_f12cc57cfa544d218ac6c26f9aae5797"&gt;three and a half years&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As illustrated above, at September 30, 2022, 97 percent of our available-for-sale securities had a maturity of less than two years.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;All of our available-for-sale debt securities are available to us for use in our current operations. As a result, we categorize all of these securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date. This reflects our intention to use the proceeds from the sale of these investments to fund our operations, as necessary.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We invest in available-for-sale securities&lt;/span&gt; with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard &amp;amp; Poor&#x2019;s, or S&amp;amp;P, Moody&#x2019;s or Fitch, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At September 30, 2022, we had an equity ownership interest of less than 20 percent in eight private companies and three public companies with which we conduct business.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following is a summary of our investments (in thousands):&lt;/div&gt;

&lt;div style="text-align: left;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;"&gt;Amortized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;September 30, 2022&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Available-for-sale securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;487,666&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,327&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;482,340&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,987&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,686&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;103,313&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;462,475&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,761&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;458,736&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,059&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(797&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,262&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,040&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(76&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,964&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,133,227&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;35&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,647&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,121,615&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;258,362&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(12,654&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;245,714&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,987&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,541&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,454&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;298,431&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,247&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;292,197&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,591&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(540&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,053&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;600,371&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;29&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(20,982&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;579,418&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,733,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,629&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,701,033&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Equity securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,097&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,841&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,256&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Privately held equity securities included in deposits and other assets (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,115&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,257&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;40,372&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;38,212&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,257&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,841&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47,628&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,771,810&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,321&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(40,470&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,748,661&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;"&gt;Amortized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;December 31, 2021&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Available-for-sale securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;383,870&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;728&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(226&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;384,372&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,493&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(18&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,494&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,424&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(64&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,360&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(37&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,778&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;612,557&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;792&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(345&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;613,004&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;382,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;331&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,644&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;379,687&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,935&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(561&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,374&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,635&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(500&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,274&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,909&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(224&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,686&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,136&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(37&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;638,615&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;471&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,966&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;635,120&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,251,172&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,263&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,311&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,248,124&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Equity securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,145&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,205&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Privately held equity securities included in deposits and other assets (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,615&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,707&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,322&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,512&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,852&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50,527&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,278,684&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,115&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,148&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,298,651&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Includes investments classified as cash equivalents in our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the nine months ended&#160;September 30, 2022, we recognized a $10.9 million unrealized non-cash loss in our condensed consolidated statement of operations related to a decrease in the fair value of our investments in publicly traded companies.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at&lt;/span&gt; cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following is a summary of our investments we consider to be temporarily impaired at September 30, 2022 (in thousands, except for number of investments).&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Less than 12 Months of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;More than 12 Months of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total Temporary&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Impairment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Investments&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;397&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;591,245&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,897&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;133,763&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,084&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;725,008&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(17,981&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,640&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(875&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53,299&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,352&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;122,939&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,227&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;643,231&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(8,327&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52,767&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;695,998&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,008&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;40,160&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(658&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,769&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(679&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;61,929&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,337&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;994&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(12&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,970&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(64&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,964&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(76&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total temporarily impaired securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;644&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,345,270&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(20,769&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;266,568&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,860&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,611,838&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,629&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase rather than underlying credit deterioration for any of the issuers. We believe it is more likely than not that we will be able to hold our debt securities with declines in value to maturity. Therefore, we anticipate full recovery of our debt securities&#x2019; amortized cost basis at maturity.&lt;/div&gt;
</us-gaap:InvestmentTextBlock>
    <us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock
      contextRef="c20220101to20220930"
      id="Text_88180c6e643a4b7eb3d2e8e8e7abb05a">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2022:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;One year&lt;/span&gt; or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;66&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After &lt;span style="text-indent: 0pt;"&gt;one year&lt;/span&gt; but within &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt; but within &lt;span style="text-indent: 0pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_f12cc57cfa544d218ac6c26f9aae5797"&gt;three and a half years&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock>
    <ions:MaximumContractMaturityPeriodRange1
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    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage
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      id="Fact_26a36804df4340729bec0b2f463acda4"
      unitRef="U003">0.66</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage>
    <ions:MaximumContractMaturityPeriodRange1
      contextRef="c20220101to20220930"
      id="Fact_3bd993e525784a5398b297b7856fe228">P1Y</ions:MaximumContractMaturityPeriodRange1>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20220101to20220930"
      id="Fact_beb1ea76eb4a4045aff26b90fc4a4ee3">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage
      contextRef="c20220930"
      decimals="2"
      id="Fact_b3c2ee50dd694d208197df43360458a9"
      unitRef="U003">0.31</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage>
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      id="Fact_812c571149d64b329fe4410606d76c7a">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage
      contextRef="c20220930"
      decimals="2"
      id="Fact_8cd01e7f5688446294ec6f1b2d7e38df"
      unitRef="U003">0.03</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage
      contextRef="c20220930"
      decimals="2"
      id="Fact_6217a171f5784696968b178278e97ffa"
      unitRef="U003">1</ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage
      contextRef="c20220930"
      decimals="2"
      id="Fact_ecfa1cb8a4484b48a192e8436b1431fe"
      unitRef="U003">0.97</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20220101to20220930"
      id="Fact_34c87d75876e42c988ffebc06f56b6a3">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20220930"
      decimals="INF"
      id="Fact_b7edbc55e46842cb916a4ced56279788"
      unitRef="U010">8</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20220930"
      decimals="INF"
      id="Fact_8144a98eb4174391a5f3065f3f804da4"
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    <us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock
      contextRef="c20220101to20220930"
      id="Text_b7c74c13c32e406597a8b0ef49047c5a">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following is a summary of our investments (in thousands):&lt;/div&gt;

&lt;div style="text-align: left;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;"&gt;Amortized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;September 30, 2022&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Available-for-sale securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;487,666&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,327&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;482,340&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,987&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,686&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;103,313&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;462,475&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,761&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;458,736&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,059&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(797&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,262&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,040&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(76&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,964&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,133,227&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;35&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,647&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,121,615&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;258,362&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(12,654&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;245,714&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,987&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,541&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,454&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;298,431&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,247&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;292,197&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,591&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(540&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,053&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;600,371&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;29&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(20,982&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;579,418&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,733,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,629&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,701,033&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Equity securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,097&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,841&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,256&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Privately held equity securities included in deposits and other assets (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,115&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,257&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;40,372&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;38,212&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,257&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,841&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47,628&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,771,810&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,321&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(40,470&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,748,661&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;"&gt;Amortized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;December 31, 2021&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Available-for-sale securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;383,870&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;728&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(226&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;384,372&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,493&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(18&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,494&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,424&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(64&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,360&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(37&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,778&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;612,557&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;792&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(345&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;613,004&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;382,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;331&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,644&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;379,687&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,935&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(561&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,374&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,635&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(500&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,274&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,909&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(224&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,686&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,136&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(37&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;638,615&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;471&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,966&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;635,120&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,251,172&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,263&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,311&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,248,124&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Equity securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,145&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,205&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Privately held equity securities included in deposits and other assets (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,615&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,707&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,322&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,512&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,852&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50,527&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,278,684&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,115&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,148&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,298,651&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Includes investments classified as cash equivalents in our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the nine months ended&#160;September 30, 2022, we recognized a $10.9 million unrealized non-cash loss in our condensed consolidated statement of operations related to a decrease in the fair value of our investments in publicly traded companies.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at&lt;/span&gt; cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following is a summary of our investments we consider to be temporarily impaired at September 30, 2022 (in thousands, except for number of investments).&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Less than 12 Months of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;More than 12 Months of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total Temporary&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Impairment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Investments&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;397&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;591,245&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,897&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;133,763&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,084&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;725,008&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(17,981&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,640&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(875&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53,299&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,352&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;122,939&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,227&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;643,231&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(8,327&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52,767&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;695,998&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,008&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;40,160&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(658&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,769&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(679&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;61,929&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,337&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;994&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(12&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,970&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(64&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,964&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(76&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total temporarily impaired securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;644&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;266,568&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,860&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,611,838&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,629&lt;/div&gt;&lt;/td&gt;
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  &lt;/tr&gt;
&lt;/table&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;4.&#160; Fair Value Measurements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1, defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly held biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions, which includes our investments in equity securities in privately held biotechnology companies. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following tables present the major security types we held at September 30, 2022 and December 31, 2021 that we regularly measure and carry at fair value. As of December 31, 2021, one of &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;our investments in publicly held biotechnology companies was subject to trading restrictions that ended in the third quarter of 2022; as a result, we included a lack of marketability discount in valuing this investment, which is a Level 3 input.&lt;/span&gt; The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 8pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30, 2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;231,960&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;231,960&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;728,054&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;728,054&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,767&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,767&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;750,933&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;750,933&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;85,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;85,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (3)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,964&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,964&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,256&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,256&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,940,249&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;990,149&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;950,100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 8pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;541,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;541,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;764,059&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;764,059&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182,634&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182,634&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (5)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,464&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,464&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (3)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,205&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,875&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,807,528&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;727,708&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,065,490&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following footnotes reference lines in our condensed consolidated balance sheet:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in cash and cash equivalents in our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$23.5 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in short-term investments.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$10.0 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$2.3 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Convertible Notes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our 0.125% Notes and 0% Notes had a fair value of $498.7 million and $631.8 million at September 30, 2022, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.&lt;/div&gt;
</us-gaap:FairValueDisclosuresTextBlock>
    <us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock
      contextRef="c20220101to20220930"
      id="Text_3fc22c693e28451987436214b4939105">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following tables present the major security types we held at September 30, 2022 and December 31, 2021 that we regularly measure and carry at fair value. As of December 31, 2021, one of &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;our investments in publicly held biotechnology companies was subject to trading restrictions that ended in the third quarter of 2022; as a result, we included a lack of marketability discount in valuing this investment, which is a Level 3 input.&lt;/span&gt; The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 8pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30, 2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;231,960&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;231,960&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;728,054&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;728,054&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,767&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,767&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;750,933&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;750,933&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;85,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;85,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (3)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,964&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,964&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,256&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,256&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,940,249&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;990,149&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;950,100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 8pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;541,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;541,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;764,059&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;764,059&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182,634&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182,634&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (5)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,464&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,464&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (3)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,205&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,875&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,807,528&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;727,708&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,065,490&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following footnotes reference lines in our condensed consolidated balance sheet:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in cash and cash equivalents in our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$23.5 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in short-term investments.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$10.0 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$2.3 million was included in cash and cash equivalents in our condensed consolidated balance sheet, with the difference included in short-term investments in our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -45pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;5.&#160; Income Taxes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning in 2022, the Tax Cuts and Jobs Act of 2017, or TCJA, requires taxpayers to amortize research and development expenditures over five years pursuant to Internal Revenue Code, or IRC, Section 174. Although the U.S. Congress is considering legislation that would defer the amortization requirement to later years, we have no assurance that the provision will be repealed or otherwise modified. Since we expect taxable income in 2022, we recorded income tax expense of $0.3 million and $3.6 million for the three months and nine months ended September 30, 2022, respectively, compared to income tax benefit of $1.3 million and $0.9 million for the same periods in 2021.&lt;/div&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;6.&#160; Collaborative Arrangements and Licensing Agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Below, we have included our Biogen, Roche and Bayer collaborations, which are our only collaborations with substantive changes during &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2022&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;December 31, 2021&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Strategic Partnership&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Biogen&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#x2019;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. We and Biogen are currently developing numerous investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, SMA, Angelman Syndrome, Alzheimer&#x2019;s disease&lt;sub&gt;&#160;&lt;/sub&gt;and Parkinson&#x2019;s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through September 30, 2022, we have received $3.4 billion from our Biogen collaborations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three and nine months ended September 30, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties (commercial revenue)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;61.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;66.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;175.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;198.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;84.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue from our relationship with Biogen&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;89.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;84.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;259.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;262.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our condensed consolidated balance sheet at September 30, 2022 and December 31, 2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;included deferred revenue of $360.2 million and $407.5 million, respectively, related to our relationship with Biogen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the third quarter of 2022, we earned $13 million in milestone payments from Biogen when Biogen advanced two targets under our neurology collaborations. We recognized one of these milestone payments in full in the third quarter of 2022 because we did not have any remaining performance obligations related to the milestone payment. We added the other payment to the transaction price and allocated it to our R&amp;amp;D services performance obligation for the 2012 neurology collaboration. We are recognizing revenue for our R&amp;amp;D services performance obligation over our estimated period of performance. We will achieve the next payment of up to $10 million if Biogen advances another medicine under our 2013 strategic neurology collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Roche&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have two collaborations with Roche, one to develop &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt; for the treatment of complement-mediated diseases, and one to &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;develop &lt;/span&gt;treatments for Huntington's disease, or HD.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In October 2018, we entered into a collaboration agreement with Roche to develop IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We are currently conducting Phase 2 studies in &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; disease indications for IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the treatment of patients with geographic atrophy, or GA, the advanced stage of dry AMD, and a &lt;/span&gt;&lt;span style="-sec-ix-hidden:Fact_37bb84ab38b14330b8b82ce65b069cf8"&gt;second&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the treatment of patients with immunoglobulin A nephropathy, or IgAN. After positive data from a Phase 2 clinical study, Roche licensed IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in July 2022 for $&lt;/span&gt;35&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and &lt;/span&gt;plans to advance &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt; into Phase 3 development for patients with IgAN&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. As a result, Roche is responsible for global development, regulatory and commercialization activities and costs for the Phase 3 IgAN study of IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We will continue to lead and conduct the open label Phase 2 study in patients with IgAN and the Phase 2 study in patients with GA&lt;/span&gt;. In July 2022, we amended our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt; collaboration agreement with Roche. The amendment changed future potential milestone payments we could receive under the collaboration. We determined there were no changes that would require adjustments to revenue we previously recognized. Under our amended collaboration agreement, we are eligible to receive up to $145 million in development milestones, $279 million in regulatory milestones and $280 million in sales-related milestone payments. In addition, we are also eligible to receive tiered royalties from the high teens to 20 percent on net sales.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under the collaboration agreement with Roche to develop treatments for HD, we discovered and developed tominersen, an investigational medicine targeting huntingtin, or HTT, protein, through completion of our Phase 1/2 clinical study in people with early stage HD. In the fourth quarter of 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. Roche is responsible for all global development, regulatory and commercialization activities and costs for tominersen. In March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest HD based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded iDMC. In January 2022, Roche announced it is actively preparing to initiate a new Phase 2 study of tominersen in patients with HD. Post-hoc analyses from the GENERATION HD1 study suggested tominersen may benefit younger adult patients with lower disease burden. From inception through September 30, 2022, we have received $283 million from our Roche collaborations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three and nine months ended September 30, 2022 and 2021, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our condensed consolidated balance sheet at September 30, 2022 and December 31, 2021 included deferred revenue of $23.6 million and $31.6 million, respectively, related to our relationship with Roche.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As discussed above, in the third quarter of 2022, we earned a $35 million payment from Roche when Roche licensed IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt;. We recognized the license fee as revenue in the third quarter of 2022 because Roche had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Roche. We will achieve the next payment of up to $90 million if Roche advances a medicine under our IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt; collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Bayer&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI&lt;sub&gt;Rx&lt;/sub&gt; for the prevention of thrombosis. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI&lt;sub&gt;Rx&lt;/sub&gt;, initiate development of fesomersen, an investigational LIgand-Conjugated Antisense medicine we designed to inhibit the production of Factor XI, and license fesomersen to Bayer. In the fourth quarter of 2022, Bayer communicated to us that it will discontinue the clinical development program for fesomersen and return fesomersen to us. We have received over $190 million from Bayer over the term of this collaboration.&lt;/div&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three and nine months ended September 30, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties (commercial revenue)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;61.6&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;66.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;175.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;198.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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  &lt;tr&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;84.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue from our relationship with Biogen&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;89.0&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;84.0&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;259.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;262.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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  &lt;tr&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71&lt;/div&gt;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three and nine months ended September 30, 2022 and 2021, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;7. Convertible Debt&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0 Percent&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Convertible Senior Notes and Call Spread&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In April 2021, we completed a $632.5 million offering of convertible senior notes. We used a portion of the net proceeds from the issuance of the 0% Notes to repurchase $247.9 million in principal of our 1% Notes for $257.0 million.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At September 30, 2022, we had the following &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes outstanding (amounts in millions except interest rate and price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;632.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde"&gt;April 2026&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.84&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76.39&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% Notes by increasing the effective conversion price on our 0% Notes. We increased our effective conversion price to $76.39 with the same number of underlying shares as our 0% Notes. The call spread cost us $46.9 million, of which $136.7 million was for the note hedge purchase, offset by $89.8 million we received for selling the warrants. Similar to our 0% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the 0% Notes. The note hedges will expire upon maturity of the 0% Notes, or April 2026. The note hedges and warrants are separate transactions and are not part of the terms of our 0% Notes. The holders of the 0% Notes do not have any rights with respect to the note hedges and warrants.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our condensed consolidated balance sheet. See our Call Spread accounting policy in Note 2, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies&lt;/span&gt;, in the Notes to the Condensed Consolidated Financial Statements. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;0.125 Percent Convertible Senior Notes and Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At September 30, 2022, we had the following 0.125% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;0.125% Notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;548.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec"&gt;December 2024&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;83.28&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;123.38&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In conjunction with the issuance of our &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes in December 2019, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our &lt;/span&gt;0.125% Notes by increasing the effective conversion price on our 0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We increased our effective conversion price to $&lt;/span&gt;123.38&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; with the same number of underlying shares as our &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes. The call spread cost us $&lt;/span&gt;52.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, of which $&lt;/span&gt;108.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million was for the note hedge purchase, offset by $&lt;/span&gt;56.1&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million we received for selling the warrants. Similar to our &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The note hedges will expire upon maturity of the &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The holders of the &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; do not have any rights with respect to the note hedges and warrants.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our condensed consolidated balance sheet. See our Call Spread accounting policy in Note 2, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies&lt;/span&gt;, in the Notes to the Condensed Consolidated Financial Statements. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;1 Percent Convertible Senior Notes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In April 2021, we repurchased $247.9 million in aggregate principal amount of our 1% Notes in privately negotiated transactions. As a result of the repurchase, we recognized an $8.6 million loss on early retirement of debt in the second quarter of 2021, reflecting the early retirement of a significant portion of our 1% Notes. The loss on the early retirement of our debt is the difference between the amount paid to retire our 1% Notes and the net carrying balance of the liability at the time that we retired the debt. We paid the remaining principal balance of our 1% Notes with $62.0 million of cash at maturity in November 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Other Terms of Convertible Senior Notes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The &lt;/span&gt;0%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to &lt;/span&gt;100 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.&lt;/span&gt; The 1% Notes were subject to similar terms.&lt;/div&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At September 30, 2022, we had the following &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes outstanding (amounts in millions except interest rate and price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;632.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde"&gt;April 2026&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.84&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76.39&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ConvertibleDebtTableTextBlock>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
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    <us-gaap:DebtInstrumentCarryingAmount
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      decimals="-5"
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      decimals="-5"
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      unitRef="U002">11000000</us-gaap:DeferredFinanceCostsNet>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_dce4bbae7b2a40908908ca4da1034984"
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    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
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      decimals="3"
      id="Fact_e393d99c85b54051913a784296da3887"
      unitRef="U003">0.005</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
    <us-gaap:DebtInstrumentConvertibleConversionPrice1
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      decimals="2"
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    <ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread
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      id="Fact_b9aacb5cbdd246a29518869cf1580bba"
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    <ions:DebtInstrumentConvertibleSharesSubjectToConversion
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      id="Fact_36af5452ef2d4158ba6f36e437b52979"
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220930_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
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      id="Fact_36a469c4005348aa8141ff489585a08c"
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    <us-gaap:ProceedsFromIssuanceOfWarrants
      contextRef="c20210401to20210430"
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At September 30, 2022, we had the following 0.125% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;0.125% Notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;548.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec"&gt;December 2024&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;123.38&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6&lt;/div&gt;&lt;/td&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;8. Legal Proceedings&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;On &lt;/span&gt;August 5, 2021,&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;four&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; purported former stockholders of Akcea filed an action in the Delaware Court of Chancery captioned John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al., C.A. &lt;/span&gt;No&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. &lt;/span&gt;2021-0681&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, or the Delaware Action. The plaintiffs in the Delaware Action asserted claims against (i) former members of Akcea&#x2019;s board of directors; and (ii) Ionis, or collectively, the Defendants. The plaintiffs asserted putatively direct claims on behalf of a purported class of former Akcea stockholders. The plaintiffs in the Delaware Action asserted that the Defendants breached their fiduciary duties in connection with the &lt;/span&gt;October 2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; take-private transaction that Ionis and Akcea entered into, in which Akcea became a wholly-owned subsidiary of Ionis. We believe this lawsuit is without merit. However, the outcome of this lawsuit or any other lawsuit that may be filed challenging the &lt;/span&gt;October 2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; take-private transaction is uncertain. Accordingly, on &lt;/span&gt;June 3, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, the parties reached an agreement in principle to settle the Delaware Action for $&lt;/span&gt;12.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million. A Stipulation and Agreement of Compromise, Settlement and Release, or the Stipulation and Settlement Agreement reflecting the terms of the proposed settlement was executed and filed with the Delaware Court of Chancery on &lt;/span&gt;July 5, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. On &lt;/span&gt;October 11, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, the Delaware Court of Chancery entered an Order and Final Judgment, or the Order, approving the Stipulation and Settlement Agreement in full after determining that the Stipulation and Settlement Agreement was fair, reasonable, and adequate. The Order provides for the full settlement, satisfaction, compromise and release of all claims that were asserted in the Delaware Action. The Order contains &lt;/span&gt;no&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; admission of wrongdoing on the part of any of the Defendants. We recorded a legal reserve of $&lt;/span&gt;12.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and the corresponding litigation settlement expense within other expense in the accompanying condensed consolidated statements of operations in the &lt;/span&gt;second&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; quarter of &lt;/span&gt;2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the proposed litigation settlement. In &lt;/span&gt;the third quarter of 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we received insurance contributions toward the settlement in the amount of $&lt;/span&gt;4.8&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million from our insurance carriers. We recorded the insurance contributions as a reduction to the litigation settlement expense in the &lt;/span&gt;third&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; quarter of &lt;/span&gt;2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;On &lt;/span&gt;January 19, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, a purported stockholder of Ionis filed a stockholder derivative complaint in the Delaware Court of Chancery captioned Leo Shumacher, et al. v. Joseph Loscalzo, et al., C.A. &lt;/span&gt;No&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. &lt;/span&gt;2022-0059&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, or the Shumacher Action. The complaint names Ionis' board of directors, or the Board, as defendants and names Ionis as a nominal defendant. The Shumacher Action Plaintiff asserts a breach of fiduciary duty claim against the Board for awarding and receiving allegedly excessive compensation. The Shumacher Action Plaintiff also asserts an unjust enrichment claim against the non-executive directors as a result of the compensation they received. The complaint seeks, among other things, damages, restitution, attorneys&#x2019; fees and costs, and such other relief as deemed just and proper by the court. On &lt;/span&gt;March 18, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we and the Board moved to dismiss the complaint. On &lt;/span&gt;May 24, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, the parties entered into a Stipulation and Agreement of Compromise, Settlement and Release.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;On &lt;/span&gt;May 25, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, another purported stockholder of Ionis filed a stockholder derivative complaint also in the Delaware Court of Chancery captioned Robert S. Cohen, et al. v. Joseph Loscalzo, et al., C.A. &lt;/span&gt;No&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. &lt;/span&gt;2022-0453&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, or the Cohen Action. The complaint names the Board as defendants and names Ionis as a nominal defendant. The Cohen Action Plaintiff asserts claims for breach of fiduciary duty, unjust enrichment, aiding and abetting breaches of fiduciary duty, and waste against the Board for awarding and receiving allegedly excessive non-executive director compensation for the years &lt;/span&gt;2018, 2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, and &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. On &lt;/span&gt;June 2, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, the Cohen Action Plaintiff filed a motion to consolidate the related Cohen Action and Shumacher Action. On &lt;/span&gt;July 5, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, the Court denied the motion to consolidate in favor of the settlement pending in the Shumacher Action.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;On July 18, 2022, we filed a Form 8-K disclosing the pending settlement and attaching the Notice of Pendency of Settlement of Action. On September 21, 2022, the Court held a hearing to consider whether the terms of the settlement should be approved, at which hearing the Cohen Action plaintiff objected to the settlement. At the conclusion of the hearing, the Court declined to approve the settlement and directed the parties to meet and confer on the issue of the scope of the release. We and our Board have denied, and continue to deny, any and all allegations of wrongdoing or liability asserted in the Shumacher and Cohen Actions.&lt;/div&gt;
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end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
