<SEC-DOCUMENT>0000874015-24-000187.txt : 20240801
<SEC-HEADER>0000874015-24-000187.hdr.sgml : 20240801
<ACCEPTANCE-DATETIME>20240801165719
ACCESSION NUMBER:		0000874015-24-000187
CONFORMED SUBMISSION TYPE:	10-Q
PUBLIC DOCUMENT COUNT:		69
CONFORMED PERIOD OF REPORT:	20240630
FILED AS OF DATE:		20240801
DATE AS OF CHANGE:		20240801

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			IONIS PHARMACEUTICALS INC
		CENTRAL INDEX KEY:			0000874015
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		ORGANIZATION NAME:           	03 Life Sciences
		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:		241167612

	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 6-30-2024
<TEXT>
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<div>UNITED STATES</div>
</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 18pt; font-weight: bold;">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>

  <div><br/>
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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 18pt; font-weight: bold;">Form <ix:nonNumeric name="dei:DocumentType" id="Fact_2df2819581474e96b1fcd81460d30dc9" contextRef="c20240101to20240630">10-Q</ix:nonNumeric></div>

  <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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</table>
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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">For the Quarterly Period Ended <ix:nonNumeric name="dei:DocumentPeriodEndDate" id="Fact_32537161ba4d4314a09cf6eba45695f5" contextRef="c20240101to20240630" format="ixt:date-monthname-day-year-en">June 30, 2024</ix:nonNumeric></div>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF SECURITIES EXCHANGE ACT OF 1934</div>
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</table>
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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">For the transition period from _____ to _____</div>

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    <td style="width: 32.84%; vertical-align: top;">&#160;</td>

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</table>
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  </div>

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


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    <td style="width: 48.93%; vertical-align: top;">
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    <td style="width: 48.93%; vertical-align: top;">
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    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>

    <td style="width: 48.93%; vertical-align: top;">
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  <div style="text-align: center;"><br/>
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    <td style="width: 2%; vertical-align: bottom;">&#160;</td>

    <td style="width: 49%; vertical-align: bottom;">
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  <tr>

    <td style="width: 49%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Address of Principal Executive Offices)</div>
        </td>

    <td style="width: 2%; vertical-align: bottom;">&#160;</td>

    <td style="width: 49%; vertical-align: top;">
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</table>
  <div style="text-align: center;"><br/>
  </div>

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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Registrant&#8217;s telephone number, including area code)</div>

  <div style="text-align: center;"><br/>
  </div>

  <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>

  <div><br/>
  </div>

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    <td style="width: 37.58%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Title of each class</div>
        </td>

    <td style="width: 2.08%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19.43%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Trading symbol</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom;">&#160;</td>

    <td style="width: 38.96%; vertical-align: bottom; border-bottom: #000000 2px solid;">
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  </tr>

  <tr>

    <td style="width: 37.58%; vertical-align: bottom; border-top: #000000 2px solid;">
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    <td style="width: 2.08%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19.43%; vertical-align: bottom; border-top: #000000 2px solid;">
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    <td style="width: 1.94%; vertical-align: bottom;">&#160;</td>

    <td style="width: 38.96%; vertical-align: bottom; border-top: #000000 2px solid;">
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        </td>

  </tr>


</table>
  <div style="text-align: left; text-indent: 18pt;"><br/>
  </div>

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


  <tr>

    <td style="width: 32.84%; vertical-align: top;">&#160;</td>

    <td style="width: 34.31%; vertical-align: top; border-bottom: #000000 2px solid;">&#160;</td>

    <td style="width: 32.84%; vertical-align: top;">&#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;">Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities
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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;">Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted and posted
    pursuant to Rule 405 of Regulation S-T (&#167;232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). <ix:nonNumeric name="dei:EntityInteractiveDataCurrent" id="Fact_9d7cd2dfc9d04988851f763df889575f" contextRef="c20240101to20240630">Yes</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9746;</span> No <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9744;</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 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>

  <div><br/>
  </div>

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


  <tr>

    <td style="width: 50%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:EntityFilerCategory" id="Fact_2589e2eea74b42479a921ff4244b06f6" contextRef="c20240101to20240630">Large Accelerated Filer</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9746;</span></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;">Accelerated Filer <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9744;</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 50%; vertical-align: top;">&#160;</td>

    <td style="width: 50%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 50%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-accelerated Filer <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9744;</span></div>
        </td>

    <td style="width: 50%; vertical-align: top;">
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        </td>

  </tr>

  <tr>

    <td style="width: 50%; vertical-align: top;">&#160;</td>

    <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_fd230472245e4f839805349dd56ecf3b" contextRef="c20240101to20240630" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric></span></div>
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  </tr>


</table>
  <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
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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;">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
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  <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 July 26, 2024 was <ix:nonFraction name="dei:EntityCommonStockSharesOutstanding" id="Fact_6036173c5d5d426ba1b4825de621ee35" contextRef="c20240726" unitRef="U001" decimals="INF" scale="0" format="ixt:num-dot-decimal">146,211,091</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>

  <div><br/>
  </div>

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


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    <td style="width: 9.24%; 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: 82.75%; 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: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; 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>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; 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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#BalanceSheet">Condensed Consolidated Balance
              Sheets</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> as of </span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited) and </span>December 31, 2023</div>
        </td>

    <td style="width: 8.01%; 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>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; 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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#IncomeStatementQ2Q3">Condensed Consolidated
              Statements of Operations</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the </span>three and six months<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> ended </span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></div>
        </td>

    <td style="width: 8.01%; 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>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; 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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#ComprehensiveLossQ2Q3">Condensed Consolidated
              Statements of Comprehensive Loss</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the </span>three and six months<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> ended </span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></div>
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    <td style="width: 8.01%; 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>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; 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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#EquityQ1">Condensed Consolidated Statements of
              Stockholders&#8217; Equity</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the </span>three and six months<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> ended </span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></div>
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    <td style="width: 8.01%; 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>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; 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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#CashFlows">Condensed Consolidated Statements of
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        </td>

    <td style="width: 8.01%; 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>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; 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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Notes">Notes to Condensed Consolidated Financial
              Statements (unaudited)</a></div>
        </td>

    <td style="width: 8.01%; 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>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item2MDAQ2Q3">Management&#8217;s Discussion and Analysis of Financial
              Condition and Results of Operations</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">:</span></span></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; 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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#OverviewQ2">Overview</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; 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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#CriticalAccountingEstimatesQ2">Critical
              Accounting Estimates</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; 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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#ResultsofOperationsQ2Q3">Results of Operations</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; 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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#LiquidityQ2Q3">Liquidity and Capital Resources</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item3MarketRisk">Quantitative and Qualitative Disclosures about Market
              Risk</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item4Controls">Controls and Procedures</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#PARTII">OTHER INFORMATION</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#ITEM1">Legal Proceedings</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#ITEM1A">Risk Factors</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#ITEM2">Unregistered Sales of Equity Securities and Use of Proceeds</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#ITEM3">Default upon Senior Securities</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#ITEM4">Mine Safety Disclosures</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#ITEM5">Other Information</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#ITEM6">Exhibits</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">51</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 91.99%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;" href="#SIGNATURES">SIGNATURES</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52</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/>
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      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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;">PART I &#8212; FINANCIAL INFORMATION</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="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: 72pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 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-weight: bold;">FINANCIAL STATEMENTS</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;"><a id="BalanceSheet"><!--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 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 cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 4.5pt;"><span style="text-indent: 0pt;">December 31</span>,</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(unaudited)</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASSETS</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#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;">Current assets:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#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;">Cash and cash equivalents</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsAtCarryingValue" id="Fact_58ab72fa50f24ffe98199f48fbe2c7f0" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">293,993</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsAtCarryingValue" id="Fact_a0cb8c640e1a44688ea7c7919293748f" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">399,266</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Short-term investments</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShortTermInvestments" id="Fact_05d3c63942424d44b3a45d0e399d7509" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,784,693</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShortTermInvestments" id="Fact_40b92a7d67634da98603b4b62a18fd2a" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,931,935</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Contracts receivable</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerAssetNetCurrent" id="Fact_42eb7b27d7ea459086945663ae763056" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,259</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerAssetNetCurrent" id="Fact_90c87b1639e7454d862938e1695fb4ba" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">97,778</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Inventories</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_bdc1851ec3a24426938e66ad4005713a" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,723</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_efd195f3edec4c3091ff79a53462abb8" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,425</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </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;">Other current assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAssetsCurrent" id="Fact_c0fa7bfa145e4eada7d79dd483724b5a" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">194,715</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAssetsCurrent" id="Fact_a989f48740884b3f9c662b56d8ec6f22" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">184,449</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Total current assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsCurrent" id="Fact_4a277ae70920496a859de16b126a781a" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,329,383</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Property, plant and equipment, net</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentNet" id="Fact_4cf8028d82514177b93946aa1df7c264" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">75,902</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentNet" id="Fact_5ad23e93b4e4467b9feec47f0d291fee" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">71,043</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Right-of-use assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAsset" id="Fact_179ff6a866a84b438c8efa61e8abcbf5" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">166,939</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </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: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deposits and other assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Assets" id="Fact_bacec939ac84418cbf35df017212761d" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,990,072</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">LIABILITIES AND STOCKHOLDERS&#8217; EQUITY</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Current liabilities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Accounts payable</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccountsPayableCurrent" id="Fact_e36e66d0552f404099023f535d194dfe" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,243</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Accrued compensation</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeRelatedLiabilitiesCurrent" id="Fact_552968f4f2a9496e83f175a2ee89b95c" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">35,018</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeRelatedLiabilitiesCurrent" id="Fact_e06d0b21026d4d1db2ff5f69431f6629" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">67,727</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Accrued liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_2fefcdea93734fcd9274bd7403d639f5" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">114,330</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_213f5a6701c24aa0979bad8e60ab97c3" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">147,894</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedIncomeTaxesCurrent" id="Fact_2af0ce9cd98b44bd81fc94205bb5c219" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">284</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedIncomeTaxesCurrent" id="Fact_7acc385f5ade40c4a52676f52d77facb" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,151</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;"><span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5b2f928a8e0345368a218705d18d351a" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_0288ff672ab44c25bec4f0ef955d906c" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction> percent</span>
            convertible senior notes, net</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtCurrent" id="Fact_7b121b31df4c44998854c02b9263c203" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">44,422</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtCurrent" id="Fact_767d6d1677ab4411a5f10c614f66ded8" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">44,332</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Current portion of deferred contract revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityCurrent" id="Fact_f6919340d9684d009e6b85f5386a61cf" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">94,066</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityCurrent" id="Fact_e81e7c5b70864705b5636324e4f12924" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">151,128</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other current liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherLiabilitiesCurrent" id="Fact_9bb84b172b644822816811d10d6c8817" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,799</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherLiabilitiesCurrent" id="Fact_330823dfcb5b4596bac0258a82124e03" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,831</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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;">Total current liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesCurrent" id="Fact_b563c92d4e8b4add87b63f57c52a0e82" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">306,162</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesCurrent" id="Fact_d521a592d7c446a7b398adb17b375e32" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">448,090</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Long-term deferred contract revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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            convertible senior notes, net</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </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: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term obligations</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Liabilities" id="Fact_f7cd0990ec2c4e71bcb30f7b03262cba" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,603,386</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Stockholders&#8217; equity:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CommonStockValue" id="Fact_b57e377e7b024f69a86bf33102ea3c25" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">144</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Additional paid-in capital</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdditionalPaidInCapitalCommonStock" id="Fact_aebda853ea1647d1b274290dee09ac0f" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,303,369</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdditionalPaidInCapitalCommonStock" id="Fact_aee9cda9e03b48d4a74d89f28e31f6ec" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,215,098</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Accumulated other comprehensive loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_5df551453918447e8a86ae46f488bc1a" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">34,838</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_ce487df6de7f42f7b8c77a08d145dc67" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">32,645</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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%; 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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RetainedEarningsAccumulatedDeficit" id="Fact_e5c1467d48e84e9db875c9a95c317d68" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,004,979</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RetainedEarningsAccumulatedDeficit" id="Fact_49f9d5e423964e58bf47306bfe215fd4" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,795,911</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stockholders&#8217; equity</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_7233636d15704723b5b453128bcd0aa4" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">263,698</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_72be79b3d961421696b3c821e00a1f9b" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">386,686</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total liabilities and stockholders&#8217; equity</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesAndStockholdersEquity" id="Fact_1ff304ed0ed84581b2d4f5f331ecaa3f" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,691,128</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesAndStockholdersEquity" id="Fact_8ae3d57392c94bea981bfe93b9c946c0" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,990,072</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </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 class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">3</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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 cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0b7e92ae84094d37aed4349f19fe764e" contextRef="c20240401to20240630_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">56,743</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_82fd59906fb44bf4b175b6e556a27aac" contextRef="c20230401to20230630_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,012</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fc05c9c21bbd4d598e399567bd0f844d" contextRef="c20240101to20240630_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">95,198</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_9e31bec432124f7c8f83a4f356e361da" contextRef="c20230101to20230630_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">111,258</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">WAINUA royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_000cbd33b6a6473aa72dc4e625925737" contextRef="c20240401to20240630_ProductOrServiceAxis_WainusRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,781</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_eff3a3bad81b49119169b0dcf6c811cb" contextRef="c20230401to20230630_ProductOrServiceAxis_WainusRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b9aea6411afe4a738c421f58dfdfe02a" contextRef="c20240101to20240630_ProductOrServiceAxis_WainusRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,907</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ea548ed659af43b48bb282d83609fa0b" contextRef="c20230101to20230630_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">145,664</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development revenue:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Collaborative agreement revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_bbda1dd7b63a4ba1949f14ca0a3fe966" contextRef="c20240401to20240630_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">141,524</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5906a5b3cae144bbb52051dcfeaa1769" contextRef="c20230401to20230630_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">91,013</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_03aeb7de29d04391a5c0728fa767a837" contextRef="c20240101to20240630_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">190,870</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4f0d2ae9fede40368bb610a6f37f5eaa" contextRef="c20230101to20230630_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">129,347</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">WAINUA joint development revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d86d3bacdddb400a9a8352d413fa6a37" contextRef="c20240401to20240630_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,690</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b69380d385c24da2911ecaae0873026f" contextRef="c20230401to20230630_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">19,501</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fe115db8a777437c817026804c674d7a" contextRef="c20240101to20240630_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">22,249</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_df7718a9917c4bc98606f70a48426e9c" contextRef="c20230101to20230630_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">43,924</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fc7abdc8dfde471cb29faf8b3d03b1e5" contextRef="c20240401to20240630_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">153,214</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d18c45e0616c4b608bc566221c7d5133" contextRef="c20230401to20230630_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">110,514</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ea3d788d8e4c4ca49f0e56246a6353d6" contextRef="c20240101to20240630_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">213,119</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_946194dd265d4cea91b3510e10eec2e5" contextRef="c20230101to20230630_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">173,271</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 52%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

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  <tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 52%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment income</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InvestmentIncomeNet" id="Fact_da58b9f4560c415fa54176a35f9dc119" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,599</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InvestmentIncomeNet" id="Fact_3cd2b918be4e49c9819f80ec577fe6ea" contextRef="c20230401to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,792</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InvestmentIncomeNet" id="Fact_0ebafdf752114d83a2c0fd0c2bfc2385" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">39,419</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:InterestExpense" id="Fact_fb880ca416564e338bae394e58388b6e" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,490</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:InterestExpense" id="Fact_0c7dc3ee4a1f46e6bfbc861159f4e8a2" contextRef="c20230401to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,291</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_6f26c02b4d794378a715f6695d645664" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,296</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_ad687e3abe4145198dee0a9f5340fd65" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">36,254</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_cd194817d5e94c0b8bb698c97e717bf5" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">33,170</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gain (loss) on investments</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:GainLossOnInvestments" id="Fact_4d97e911d7e3499aae9759b83e7d5483" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">3,533</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Loss before income tax expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_b3e19e1abb90420aaf2bb12ec56c37fb" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">208,928</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_1ae0e04b97a04c6293cd632207aa3b76" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">190,390</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Income tax expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_db872921aba5410c8b6b6f3c9d42cfba" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">64</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_b08da18917ed432eb322791085b2fe69" contextRef="c20230401to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,842</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_36659a44982545939332ae10bee1f6f3" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">140</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_36f6a6512d5e4f289005ff19bd0dbb27" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">19,223</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_25084dde9fca478ab4cf8fdde476d7bb" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">66,265</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_13bca1ac46f24ac0a92b500b659b8fab" contextRef="c20230401to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">85,290</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_7a0b430f34d14a699de458b11994e9d5" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">209,068</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_2d54f47073be4a62aa55be6ca596801a" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">209,613</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Basic and diluted net loss per share</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_a0a1b4ecfec8405e86a36a3bdcb93197" contextRef="c20240401to20240630" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_46b59726a35f4dba9f55a2311fc4a8ee" contextRef="c20240401to20240630" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.45</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_fa70bedf35b84a0381603344e4b6931e" contextRef="c20230401to20230630" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_28f3bb58b3654c72a7371500e485ffc2" contextRef="c20230401to20230630" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.60</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_bba77551718249babb0bebcfec94dbbd" contextRef="c20240101to20240630" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_6ea837765f7b4b01a1043013264b8b22" contextRef="c20240101to20240630" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">1.43</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_936d3e64a0ec402f80854a67a962baec" contextRef="c20230101to20230630" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_fbf707c31d894cfba383005cdae7edfa" contextRef="c20230101to20230630" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">1.47</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </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;">Shares used in computing basic and diluted net loss per share</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_00ff0f77d486470ea08b21a4dfa1339d" contextRef="c20240401to20240630" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_1aaf11ce59bb48759ebc7e3d31ba5c31" contextRef="c20240401to20240630" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">145,958</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_cfbe0d7c81094560943b5c2d9e148660" contextRef="c20230401to20230630" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_f6086afb08384309901675568ec56316" contextRef="c20230401to20230630" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">143,098</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_94acf981aacf4f289361fa85d5dd2938" contextRef="c20240101to20240630" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_67a5cd623455410cb122f236674e7d0e" contextRef="c20240101to20240630" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">145,748</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_7d60593093d849cc93552c9324c61464" contextRef="c20230101to20230630" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_0bf80676d0ec4afc922c1f8227feecaa" contextRef="c20230101to20230630" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">142,918</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </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 class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">4</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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 cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_956abcf640b64e40a411493d69205818" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">66,265</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_47e41b95caab4e92bb28995bd44b3aad" contextRef="c20230401to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">85,290</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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  <tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_d74b567e3b014156a049c64e1307a63a" contextRef="c20230401to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,000</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_7f32c82581ad4b949e2e07adbccdd78e" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,393</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Currency translation adjustment</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_e9b531ac4e7e466f809b4e8a0d95361e" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">24</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_b162ec084f6c46ccaef6685d9c1854ba" contextRef="c20230401to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">70</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_769ab52bea87434eb4b048adcbc4add4" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">137</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_5a98d17953ba47578caa9b15a11c588f" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">174</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTax" id="Fact_065f79ada0374820bc5a6fbec88a7615" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">66,139</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTax" id="Fact_7959aba910af49989a21445262c14dde" contextRef="c20230401to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">87,220</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTax" id="Fact_5b13b78036de4cf7919d38c272156ca7" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">211,261</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTax" id="Fact_1ed5640888d44e68b7fa43735312164f" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">203,046</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </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 class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">5</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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;">(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 cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Common Stock</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Additional</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated Other</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <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>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_f460bd0aff664980870ea8e5e75a1848" contextRef="c20230331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">143</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_d4889378c8d9480b96b3dc528f1eba37" contextRef="c20230331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,089,358</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_e8e4cd7bbb904cd48d998a8bd1f6f2e2" contextRef="c20230331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,553,948</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_3f376a9efe094721acc6c84a4a71de80" contextRef="c20230331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">486,570</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </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;">Net loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_2d62c0ec11c842a1ae5716602a4b6281" contextRef="c20230401to20230630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_b6a7dd69f2a9463faae2144119abffd9" contextRef="c20230401to20230630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_c64c542925414e8c83eea2321058db98" contextRef="c20230401to20230630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_933de9acdba147e68bfe9bac7c541751" contextRef="c20230401to20230630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">85,290</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_4438030ac1ba46c988825faaa5c034af" contextRef="c20230401to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">85,290</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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%; background-color: #CCEEFF;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_e4cfabf4d1f849c1bc5036161237d550" contextRef="c20230401to20230630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_8934ac53e1df4f7489c4b96df024b26e" contextRef="c20230401to20230630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_a92d389913e147c890038453499b92d8" contextRef="c20230401to20230630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,000</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_45dd7d43b503464f9f0b0c364cd2be8a" contextRef="c20230401to20230630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_9e658ea9c0dc4a56b7e313426cab56aa" contextRef="c20230401to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,000</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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%;">
          <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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_d1aabbaae81446b0914967d0f2a70b44" contextRef="c20230401to20230630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_a80b5f0672584087b5268c8be3599f13" contextRef="c20230401to20230630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_3dad36a843ba40378664d3dccc6c0f86" contextRef="c20230401to20230630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">70</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_11acf54b8adf49129c93405a9a9a35e2" contextRef="c20230401to20230630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_ea1d443af1494feeb9c969facd4cd97a" contextRef="c20230401to20230630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_6698c6866b274e68b2b91954263cd3ea" contextRef="c20230401to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">26,561</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </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;">June 30, 2023</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_ba38bc2ac6c549c19380cdd7d23a7644" contextRef="c20230630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">143,167</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_44f1c20930ab40a4840b6a493c0c1c0d" contextRef="c20230630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">143</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_8e3ae95fed3948e6aa338f7bcc06a024" contextRef="c20230630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,118,309</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_98d86fa0ae7f464e860e56b84513348e" contextRef="c20230630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">50,913</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_1609172481c04b6fae591dd8d4ed670c" contextRef="c20230630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,639,238</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_a23dd4b0f79747e6a869f76130e772d5" contextRef="c20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">428,301</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">March 31, 2024</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_32f887af1f384adf8f9fd2b14798a9dc" contextRef="c20240331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">145,845</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_90db06954a8d4d0ba6e8307a446925cd" contextRef="c20240331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">146</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_d729ddf413884aada9a66c8ba510ae4d" contextRef="c20240331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,270,047</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_21ce6f0e307d4eb7ba78a66d3da6e84d" contextRef="c20240331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,938,714</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_7648bfdfbf0940a4bf96a7ce13cf1ad3" contextRef="c20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">296,515</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_c88d54dc726342e4972eaefd7a051920" contextRef="c20240401to20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_9cf891be08ec4be38cb74bb1f2b5f043" contextRef="c20240401to20240630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_cdc09fc9cea84c4bb56bf39a0b0f0bb2" contextRef="c20240401to20240630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_35a1e22e0a16468e980e52ec905cdd6e" contextRef="c20240401to20240630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">66,265</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_f3fb7df78ee84b679a9455a24c8868ed" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">66,265</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized gains, net of tax</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_11314cebb76149f4a608afac24ac04b8" contextRef="c20240401to20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_7b0eb56cbf6c4876adbb9cd78cb7fab3" contextRef="c20240401to20240630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_e9bf727feb074c6d81eadada30431fc1" contextRef="c20240401to20240630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">150</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_4f7972f7ccc845178dd50c3adeba7bea" contextRef="c20240401to20240630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_c166701bbeab4dc6b0ef6b9ba9449b64" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">150</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </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;">Foreign currency translation</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_227d758ea4e74df1a393442ec610b305" contextRef="c20240401to20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_0b254bcc6c334e83b0fc2405839bb29a" contextRef="c20240401to20240630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_59f8cd0035bf41978b1986a44e2b9b77" contextRef="c20240401to20240630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">24</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_e0d9b726e3a74e96bb34879db9ea1ac5" contextRef="c20240401to20240630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_3ea72a4068e947c39ec89e6e3d5e6026" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">24</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance of common stock in connection with employee stock plans</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_a0997c97f0564e8ebfa4ae2be270a0ee" contextRef="c20240401to20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">180</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_6681378e601142699475f5097b49f5b3" contextRef="c20240401to20240630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,594</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_fbd10a5446f64525ad97dbee65735ca9" contextRef="c20240401to20240630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_dbb0d91398114cd388b84cf9228aaa69" contextRef="c20240401to20240630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_a62772da70e144c280cbb85410455f37" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,594</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_68081df6527740dfa26ec4797ec27aa4" contextRef="c20240401to20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_5314ac973db348bb85730f2174126923" contextRef="c20240401to20240630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">30,728</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_2b2724fdff53416ba79dd482f9ac014a" contextRef="c20240401to20240630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_9b47baa9611d4ccbb269f9f88ab523c8" contextRef="c20240401to20240630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_469cc0df4f854f08ad045ffae103da1d" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">30,728</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </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;">June 30, 2024</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_0f0be876932540309deb6071f37c6b70" contextRef="c20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">146,025</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_b71c12ae90734864a4463846ddf4a35f" contextRef="c20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">146</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_f4b8bbee549b4d698629eeec3f6d69bc" contextRef="c20240630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,303,369</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_b92a64b7192841d0ad0df25703888391" contextRef="c20240630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">34,838</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_1599b9afeae3443694982451aff023a8" contextRef="c20240630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,004,979</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_e457c14215284c388c791e447980f51c" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">263,698</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </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 class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">6</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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;">(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 cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Common Stock</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Additional</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated Other</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <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>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Paid in Capital</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <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;">December 31, 2022</span></div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_d8d0d8b279f64d2d99baad5ca491e0d8" contextRef="c20221231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">572,887</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_09f8d09c9d8c4d2c80eb0036946b4d91" contextRef="c20230101to20230630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_f499610f756c4e5784aa21bfb349b501" contextRef="c20230101to20230630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_d06e2d3f332f4064b1ef72b7b2eca49f" contextRef="c20230101to20230630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">209,613</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_917eab76c67943ddb0a2a9ad98f592c1" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">209,613</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized gains, net of tax</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_97a9ff7be914426abfc6e33676888473" contextRef="c20230101to20230630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_ed18254743184881a6bb269767cdacc5" contextRef="c20230101to20230630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,393</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_4fdc834f36d24680a883491d4337ab3f" contextRef="c20230101to20230630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_d52fb5fa826749fbaff08a3722d9010b" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,393</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </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;">Foreign currency translation</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_2b897b3c1da340f483a90d340deb21d9" contextRef="c20230101to20230630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_e0e13e77b5c049b5bd4e5b7fb3d0a10c" contextRef="c20230101to20230630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">174</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_7c527e10319541fe9773cce1af3bb834" contextRef="c20230101to20230630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_9b74f552bb894878bb0b14a4cd3c1563" contextRef="c20230101to20230630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">53,510</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_a4830c14aa194a8a942e1140d36f0157" contextRef="c20230101to20230630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_94f132fedc8340b28be09cfdb6c939af" contextRef="c20230101to20230630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_03f19dcf92d643a3b6b2f0e90bf33628" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">53,510</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </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;">June 30, 2023</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_6a3ebbc8b51447a5952b335e52c85d67" contextRef="c20230630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">143,167</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_a4b9f22a573749a498a1e1f7668420b9" contextRef="c20230630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">143</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_6ef657a89a0c48fa84e86fffe91048f6" contextRef="c20230630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,118,309</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_7705eaf5625342ad8e650600a4e19b38" contextRef="c20230630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">50,913</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_4d7a9472f516470f92a2c9a71881a8c8" contextRef="c20230630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,639,238</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_4e98f97080bb4319bae0c10d29b9f45e" contextRef="c20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">428,301</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">December 31, 2023</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_53b4ad5ff7704512b6604b9969bf85a3" contextRef="c20231231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">144,341</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_d75411219d694fb6967d82c73128b081" contextRef="c20231231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,215,098</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_abe177b8b14f4096b6d6e3a7395b511e" contextRef="c20231231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">32,645</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_8ec2ec066d47486ca42f5bef6480e27c" contextRef="c20231231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,795,911</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_83cc5fb055d9422da4c4c4e99778ab22" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">386,686</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_9cfa82793142456ea1dc943d2a9abc70" contextRef="c20240101to20240630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_76866ebc6e314b04a916df386c4bea2e" contextRef="c20240101to20240630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_3c8c391bca68421e81e7d0db1d28dc7f" contextRef="c20240101to20240630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">209,068</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_50ab0ed170c4480d82809b8f3c1f32fb" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">209,068</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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%; background-color: #CCEEFF;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_ed6ac52f45dc4a64a852665cb07aa8c7" contextRef="c20240101to20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_bd8e6af5bb804cc9a5852e9803653348" contextRef="c20240101to20240630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_6a13945323884f2b92dfd434a3f14cd9" contextRef="c20240101to20240630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,056</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_be255c9ac3c440b891510d1d114b15af" contextRef="c20240101to20240630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_9b7b69ba2377481db4cdf253828263c9" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,056</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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%;">
          <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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_5ec07a4bd14f465cadd021a22600de39" contextRef="c20240101to20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_968e834d773b4959aae802e00c2cdef8" contextRef="c20240101to20240630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_9eef51e9131e4916a79e14f067a7d0cd" contextRef="c20240101to20240630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">137</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_78b97e546ed4435fa7c9bedd7cfc96d2" contextRef="c20240101to20240630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_cb965deefe6d4d639b3f582915a38369" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">137</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance of common stock in connection with employee stock plans</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_6551b6a9356f4f8ab17a01cf99f9e2ce" contextRef="c20240101to20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,684</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_a3c349d5d8f04c7e820909a3e7c21158" contextRef="c20240101to20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_fd177618a27e45ddaa3a22e55d5712c7" contextRef="c20240101to20240630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_b186e33c605a4768a1d3ad7410a12f66" contextRef="c20240101to20240630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_2ad15f6684dd492a874f088945645aae" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">26,205</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_072aa827f085403a86e5dd0b7344a2f5" contextRef="c20240101to20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_fc2a3939f5444e82a02add1e212e5019" contextRef="c20240101to20240630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">62,068</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_9cc8734d05aa4b1abf5776974283cf5b" contextRef="c20240101to20240630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_ce326186cf914df292ad4dd783a5d6c8" contextRef="c20240101to20240630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_8468282805f6485888fa02beb3073198" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">62,068</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </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;">June 30, 2024</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_ab1b5a72d6704443ae923d4f7c3e7fc2" contextRef="c20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">146,025</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_303e394e05ca4145a59f47f98827626d" contextRef="c20240630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">146</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_6cf7c453ab9f4861bdff84a9bccec821" contextRef="c20240630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,303,369</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_d3438d70b67142c7a3a7bcc3fd453ffe" contextRef="c20240630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">34,838</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_e04b3c2d9b3b404ba5d9e43f14ca708e" contextRef="c20240630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,004,979</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_fb0f3372a43047dc81700fbf558b1a4b" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">263,698</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </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 class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">7</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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 cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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; font-weight: bold;">Operating activities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#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 loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_f7c36546ee144c2c86ebae7331367498" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">209,068</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_a21016941dc0429abc056d42872b32b2" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">209,613</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to reconcile net loss to net cash used in operating activities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Depreciation" id="Fact_100d69cecae84cbdad6e81cc7ef52262" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,013</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Depreciation" id="Fact_8c77ba4be59247e38c94131c141d0abf" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,225</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAssetAmortizationExpense" id="Fact_9e6711269ac449af9f3ea5cf3d5eaa6a" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,957</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAssetAmortizationExpense" id="Fact_5558af291e4642f9823614e737f072ce" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,826</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 other assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfIntangibleAssets" id="Fact_edc8ad178aa7466a8d83a15fca3ea881" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,260</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfIntangibleAssets" id="Fact_f8039ed914974946804216d314447463" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,244</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 discount on investments, net</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_246d1c45e9574034a56b56918f85ebb2" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">19,143</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_4aaed7ae1baf412b9dbc761309827e6d" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,481</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of debt issuance costs</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_0996ae3cb47d4deda2a70a7fe98905e0" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,338</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_0c9f58357fb646578e9fa6d8e42f1be2" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,966</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Non-cash royalty revenue related to sale of royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:RoyaltyPayments" id="Fact_6292e26423504fc0bd79e28555a6db3c" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,236</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:RoyaltyPayments" id="Fact_9ca52bba18d34c7ab9a5a77faafda7ca" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,562</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash interest related to sale of future royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:InterestExpenseRelatedToSaleOfFutureRoyalties" id="Fact_086bf64fac6b4680b15353ddeab54f26" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">35,949</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:InterestExpenseRelatedToSaleOfFutureRoyalties" id="Fact_e2859b6b5908454a9501ba4b33770396" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,915</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensation" id="Fact_04aaa2990d5a40ad8fdb1b5232b70a08" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">62,068</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensation" id="Fact_75990e27c7ef4862aef11ff7e8db6961" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">53,510</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RealizedInvestmentGainsLosses" id="Fact_14350362b48c4c63a2d02245c7bdfc8e" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,201</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RealizedInvestmentGainsLosses" id="Fact_1d0b4f23d12a4c8d93769c2560a353b7" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">301</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gain on early retirement of debt</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_68b70a415b084a83a7c16fab23bfbe46" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_49edf43521bd4652ad2a760a59951897" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,292</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash losses related to other assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_7fcd200b638b455db39131034fdc6876" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">389</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_fe5c9b55fb8549bebb24e58da0204a34" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">775</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInInventories" id="Fact_6cc57db037e24224babb23341491fa27" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">298</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherOperatingAssets" id="Fact_6beef6ad7156442b8b64be1683073767" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,381</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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;">Income taxes</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInAccruedIncomeTaxesPayable" id="Fact_920199b2a9f34fa1848e6eca1d94d87b" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,867</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Accounts payable</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInAccountsPayable" id="Fact_8a994583ad564784b70d134601567caf" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">17,064</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInAccountsPayable" id="Fact_7d0b289b5d31478faec7c1781df64a2b" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,517</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Accrued compensation</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities" id="Fact_5f5c568dfefd46649d7f965b7bc2f695" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">32,709</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities" id="Fact_e29dcd8047ff491884c92796c96013cb" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">19,856</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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 liabilities and other current liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherCurrentLiabilities" id="Fact_08f6c9cf45f246f6a33cd0c9749cb737" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">39,201</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherCurrentLiabilities" id="Fact_8da87902979a47b2b8cd9fcda264eef6" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">37,562</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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%; padding-bottom: 2px;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_5d444769c22d417199294bd747e46936" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">109,545</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_7536a4e7a5c548658c9c6c4190e7e76b" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">27,695</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <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%; padding-bottom: 2px; background-color: #CCEEFF;">
          <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 operating activities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInOperatingActivities" id="Fact_66c31f18a56f439ab964f9bf11cd801d" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,818</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInOperatingActivities" id="Fact_aaaa638d546d45448755c94c63222ccd" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">231,356</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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; font-weight: bold;">Investing activities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </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 sale of short-term investments</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" id="Fact_421423d1ea9a4d73aef63e7e59de4afb" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">968,413</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" id="Fact_6dc4fafd64864e3188177206b20e21e5" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">701,034</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquirePropertyPlantAndEquipment" id="Fact_5c4c86b4988a4bcc93f568312cf27532" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,727</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquireIntangibleAssets" id="Fact_bedfe0d50deb453aac9adee6a16b847b" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,264</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquireIntangibleAssets" id="Fact_2503d109e9bf429abba6e180534abb50" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,314</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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%; padding-bottom: 2px;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInInvestingActivities" id="Fact_92cb4d2048d14989a03cc74060fe995e" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">138,555</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInInvestingActivities" id="Fact_98c358a7d9cc4f7dbda064764db082d3" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">256,125</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <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;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_ddb0c2b46432418f9be1b92d0e804ae9" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">26,205</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_8bffc0bd215e4f839416df4a6531312e" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,950</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromConvertibleDebt" id="Fact_e18a4687c7fb4036854e1ed58e7c07f5" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromConvertibleDebt" id="Fact_793174f7c2924ac8b52f4e82b3e222f0" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">575,000</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <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;"><span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_d3f3d6e23b664d39a01eeffa5aafefae" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction> percent</span>
            convertible senior notes issuance costs</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsOfDebtIssuanceCosts" id="Fact_318c100eb2aa4ab49cb6eb69be07e5bb" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsOfDebtIssuanceCosts" id="Fact_7e82740f53d24afbb0967d827213dd21" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">13,658</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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: -9.15pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Repurchase of $<span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_c5ea316243964e22aef7aec2a88a66e5" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">434.1</ix:nonFraction></span>
            million principal amount of <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_02c6e8c93e3440848afaffeac0feac4d" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction> percent</span> convertible senior notes</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_72eb3286e2c248fab214ce5db2bcb24c" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_323a16434bee4a23b1ba75f90e973c08" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">420,158</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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: -9.15pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of future royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_1a7def75d8d14c729b0187e5933b26f0" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; 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;">Principal payments on mortgage debt</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RepaymentsOfSecuredDebt" id="Fact_95b149e4b1f949d691d01b7a972215e2" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">78</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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%; padding-bottom: 2px;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInFinancingActivities" id="Fact_eaaca3e288be4952adf9a7f8f7bf8f92" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">26,127</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effects of exchange rates on cash</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" id="Fact_05d7fd45bf434136a2b94742f2dddc94" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">137</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" id="Fact_44c0dad63f8b413c8cf4e5c0bbc41200" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">174</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Net increase (decrease) in cash and cash equivalents</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_381c34e8f196433d88bcc5a40e6d5ead" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">105,273</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_695ef20670484629abffb58a97885612" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">148,318</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </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;">Cash and cash equivalents at beginning of period</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_f005ffe7399e4372b86484b39e4de899" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">399,266</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_6c5f411c5f5446ed84bf5042679097db" contextRef="c20221231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">276,472</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <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 end of period</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_22fc70baf81348a4bed7f3a0cca2d925" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">293,993</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_26348b07f1404eb2b971660219ce0e2f" contextRef="c20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">424,790</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Supplemental disclosures of cash flow information:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Interest paid</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InterestPaidNet" id="Fact_1c0954c400a1482b8ec42df7704e2f57" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,569</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Supplemental disclosures of non-cash investing and financing activities:</div>
        </td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts accrued for capital and patent expenditures</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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</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>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">8</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </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;">June 30, 2024</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>

  <div><br/>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.&#160; Organization and 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; font-weight: bold;">Organization and Business Activity</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporated in California on January 10, 1989. In conjunction with our initial public offering, we reorganized as a Delaware
    corporation in April 1991. We are a leader in the discovery and development of RNA-targeted therapeutics.</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;">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 six months ended&#160;June 30, 2024 and 2023 on the same basis as the audited financial statements for the year ended December 31, 2023. 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, 2023 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="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_d751d8638e404708bbf18fb6bb90a9f5">single</span>
    segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a <span style="-sec-ix-hidden:Fact_baf534ae803246ddb035eb980683637d">single</span>
    operating segment.</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;">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 United States, or </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><br/>
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<div><ix:nonNumeric name="us-gaap:SignificantAccountingPoliciesTextBlock" id="Text_3f631d62f8b3441ca8993f923978bb09" contextRef="c20240101to20240630" escape="true" continuedAt="Text_d311515663d24201b5ed5036a82ddf191">
<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;">Our significant accounting policies have not changed substantially from those included in our Annual Report on Form 10-K for the year
    ended December 31, 2023.</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;">Recently Issued 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;">We do not expect any 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. Supplemental Financial Data</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;">Inventories</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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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30, 2024</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2023</div>
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  <tr>

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    <td valign="bottom" style="vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryRawMaterials" id="Fact_6cec13c5f4334a1ba6216a6bc406747c" contextRef="c20231231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,985</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; white-space: nowrap;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryRawMaterials" id="Fact_4a8280762bb1470eace824e402d6b623" contextRef="c20240630_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,412</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryRawMaterials" id="Fact_cf1accaf2b004921b424e5cd65e40c1f" contextRef="c20231231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,809</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF; white-space: nowrap;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryRawMaterials" id="Fact_9975fb0b2fa74f9e8ab81ebad8fb2237" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">24,623</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryRawMaterials" id="Fact_e3f1efde1cdb414796dec720e17eac54" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">22,794</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; white-space: nowrap;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryWorkInProcess" id="Fact_e7c4b729eb5c4047a12ddaf1f657b647" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,614</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryWorkInProcess" id="Fact_182d548d120f4e1daae74044c3e1bbe5" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,477</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryFinishedGoods" id="Fact_b21c128f10e14f89b4963ecd92676ea1" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">486</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryFinishedGoods" id="Fact_70a3a016ecb849cd9021230823cf224d" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">154</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; white-space: nowrap;">
          <div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventories</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_6f6a7ebaae1b4d95ace7fcfcf1fba210" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,723</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_3e4c02edf53745679ae7e698216e7837" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,425</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d1b7791c55074863be671d8f56a6458d7" continuedAt="Text_d1b7791c55074863be671d8f56a6458d8">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation></div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">9</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </div>
<div><ix:continuation id="Text_d1b7791c55074863be671d8f56a6458d8" continuedAt="Text_d1b7791c55074863be671d8f56a6458d9"><ix:nonNumeric name="us-gaap:ScheduleOfAccruedLiabilitiesTableTextBlock" id="Text_2a5416376d8f443abf966ca8534832b3" contextRef="c20240101to20240630" escape="true" continuedAt="Text_2ccd66be7ea248b88e45d3927a5188721">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>
</ix:nonNumeric></ix:continuation>

  <ix:continuation id="Text_d1b7791c55074863be671d8f56a6458d9" continuedAt="Text_d1b7791c55074863be671d8f56a6458d10"><ix:continuation id="Text_2ccd66be7ea248b88e45d3927a5188721" continuedAt="Text_2ccd66be7ea248b88e45d3927a5188722">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d1b7791c55074863be671d8f56a6458d10" continuedAt="Text_d1b7791c55074863be671d8f56a6458d11"><ix:continuation id="Text_2ccd66be7ea248b88e45d3927a5188722" continuedAt="Text_2ccd66be7ea248b88e45d3927a5188723">
<div style="display:none;"><br/></div>
<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>
</ix:continuation></ix:continuation>
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<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d1b7791c55074863be671d8f56a6458d12"><ix:continuation id="Text_2ccd66be7ea248b88e45d3927a5188724">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30, 2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Clinical development expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AccruedClinicalDevelopmentExpenses" id="Fact_9fa65e9eb4874e529d2b5a8558dbeefc" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">82,017</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AccruedClinicalDevelopmentExpenses" id="Fact_e1554d35bd0e4c82aabac0d765ba6ddc" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">105,967</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; white-space: nowrap;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In-licensing expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AccruedInLicensingFeesCurrent" id="Fact_c222f622055145968e8cd08ff3a569bd" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,603</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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</ix:continuation></ix:continuation></div>

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<div><ix:nonNumeric name="us-gaap:RevenueFromContractWithCustomerTextBlock" id="Text_1284d7033f3441c5834281acfd6f5060" contextRef="c20240101to20240630" escape="true" continuedAt="Text_b1f603df6d67420faa8a0c488a91a15d1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4. Revenues</div>
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<div><br/>
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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;">During the three and six months ended June 30, 2024 and 2023, our revenues were
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<div><br/>
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        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_574b824f1f124372a2c1825e8cc7715b" contextRef="c20230401to20230630_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,012</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b4f98bf14208471bb5215ab21e9fb071" contextRef="c20240101to20240630_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">95,198</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">WAINUA royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_9522f5d1cf674de6978d7283a4f8d39f" contextRef="c20240101to20240630_ProductOrServiceAxis_WainusRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,907</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <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;">TEGSEDI and WAYLIVRA revenue, net</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_27647a522e784368980bff289e33d4bf" contextRef="c20240101to20240630_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,704</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_71b0488640624969a289828fb8ae755f" contextRef="c20230101to20230630_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,273</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;">
          <div style="text-align: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total other commercial revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_96d2cfc12590477d93004f9faae631cd" contextRef="c20240401to20240630_ProductOrServiceAxis_OtherCommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,512</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_edbb7a7151f34522b2d829dd27d19ec0" contextRef="c20230401to20230630_ProductOrServiceAxis_OtherCommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,885</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_21a2170dfd5447988e60057caae1858a" contextRef="c20240101to20240630_ProductOrServiceAxis_OtherCommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">31,524</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5f1472e6e3814ac3b393320266011bd4" contextRef="c20230101to20230630_ProductOrServiceAxis_OtherCommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">34,406</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_89d535fbf16d488fa5543613cc331260" contextRef="c20240401to20240630_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">72,036</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3bd9a7a6495b4ea59962b110673d10bb" contextRef="c20230401to20230630_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">77,897</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c29020f995c748ca94ac726f575e39f2" contextRef="c20240101to20240630_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">131,629</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_94b90e9626144b9cac3b02f165cabb40" contextRef="c20230101to20230630_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">145,664</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development revenue:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Collaborative agreement revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fd4e60c450af4e078aee86e32800b2a5" contextRef="c20240401to20240630_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">141,524</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0b43edfc2fcd47778bd02af672a65857" contextRef="c20240101to20240630_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">190,870</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA joint development revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4d9f76097d774d279e0ebcf1b6c87969" contextRef="c20240401to20240630_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,690</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f2f25449441e45d9860b8621066c1487" contextRef="c20230401to20230630_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">19,501</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5c4da791c380484f9b1464b0cc2bdb2d" contextRef="c20240101to20240630_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">22,249</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_8a09819bb0cf4afb90c81a4b791d6723" contextRef="c20230101to20230630_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">43,924</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research and development revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_58ebe3ab161c4572b45143c584a625b3" contextRef="c20240401to20240630_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">153,214</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_a3beadb8d7c54ed6b9c787c34fb8a364" contextRef="c20230401to20230630_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">110,514</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_28eb3b3989d54f7ab800e8bebe832975" contextRef="c20240101to20240630_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">213,119</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_01de167cf4164905a374813f0e3ab0a3" contextRef="c20230101to20230630_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">173,271</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: 54pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_9253a9e4b3f4403186646873b5727efc" contextRef="c20240401to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">225,250</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f04780da48e945508d593936936e5849" contextRef="c20230401to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">188,411</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fafc09ceeaed41c7b32f440a8537e2a7" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">344,748</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_eae218a0e0bd49e6b76c5b2dee06f2c0" contextRef="c20230101to20230630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">318,935</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><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; font-weight: bold;"><span style="text-decoration: underline;">Revenue Sources</span></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;">The following are sources of revenue and when we typically recognize revenue.</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; font-style: italic;">Commercial Revenue: SPINRAZA royalties and WAINUA royalties</div>
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<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 earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. In 2024, we began earning royalties from
    WAINUA sales.</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; font-style: italic;">Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net</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;">We earn commercial revenue from TEGSEDI and WAYLIVRA sales under our distribution agreements with Sobi. In addition, we receive royalties
    from PTC Therapeutics International Limited, or PTC, for TEGSEDI&#160; and WAYLIVRA sales.</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; font-style: italic;">Commercial Revenue: Licensing and other royalty revenue</div>
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<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;">&#160;We also recognize as commercial revenue sales milestone payments and royalties we earn under our partnerships. For example, we earn
    royalty revenue on net sales of QALSODY, which is included in Licensing and other royalty revenue.</div>
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<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; font-style: italic;">Research and development revenue under collaboration agreements</div>
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<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 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>
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  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">10</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </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; font-style: italic;"><span style="text-decoration: underline;">Upfront payments:</span></span> 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. If part or all of the upfront payment is a license fee, we recognize as revenue the portion related to the license when we deliver the license to our partner because our partner has full use of
    the license and we do not have any additional performance obligations related to the license after delivery.</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; font-style: italic;"><span style="text-decoration: underline;">Milestone payments:</span></span> We
    include variable 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 R&amp;D 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, when we
    achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&amp;D services performance obligation and
    recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone payment to 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;">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.</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; font-style: italic;"><span style="text-decoration: underline;">License fees:</span></span> We 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 because our partner has full use of the license and we do not have any additional performance obligations
    related to the license after delivery.</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;">WAINUA (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 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize WAINUA for the
    treatment of transthyretin amyloidosis, or ATTR. We jointly developed and are commercializing WAINUA<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>with AstraZeneca in the U.S. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for the treatment of adults with polyneuropathy caused by hereditary ATTR, or ATTRv-PN.</span> We initially granted AstraZeneca exclusive rights to commercialize WAINUA outside the U.S., except for
    certain Latin American countries. In 2023, we expanded those rights to include Latin America. Under the terms of the agreement, we received a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_caed9448b892449d9469e087cd266fc7" contextRef="c20210101to20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" 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 WAINUA collaboration under ASC 808 and identified <ix:nonFraction name="ions:NumberOfMaterialComponents" id="Fact_829b11ec459b4832be62425f90613bde" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U006" 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 Accounting Standards Codification, or ASC, Topic 606, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span>, or ASC 606, for the license we granted to AstraZeneca and as a result we had <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_e41f149425d842f2be4dff9369996396" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation. For our sole performance obligation, we determined the transaction price was the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_2f700651d28647edaf80781f052f79f8" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" 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 Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or 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 currently responsible for <ix:nonFraction name="ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" id="Fact_428d8e2ae7744e358f8dc2831b664556" contextRef="c20240101to20240630_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" 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 WAINUA 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 selling,
    general and administrative, or SG&amp;A, expense and R&amp;D expense, respectively.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#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 AstraZeneca, Biogen, Otsuka and
      Roche collaborations, which are the collaborations with substantive changes during 2024 from those included in Part IV, Item 15, Note 4, </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;">, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2023.</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;">AstraZeneca</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 have </span><ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_fab2e70ac4764c7e96dc0a00464eea97" contextRef="c20240630_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> collaborations with AstraZeneca, </span><ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_540d06877e0e4c3a91c3be4b271d9eb4" contextRef="c20240630_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> focused on the joint development and commercialization of WAINUA and </span><ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_ab0253a10365491e9eb157736f5e1022" contextRef="c20240630_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> focused on the treatment of cardiovascular, renal and metabolic diseases. From inception through </span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received more than $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_98769e3f8d5d4f94a8313f56dee56834" contextRef="c20240630_RangeAxis_MinimumMember_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">920</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million from these collaborations.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of our WAINUA collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_1f91287fe0a848ad987236d0f6ffeeb0" contextRef="c20240630_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U002" decimals="-8" scale="9" format="ixt:num-dot-decimal">3.6</ix:nonFraction> billion, which is comprised of a $<ix:nonFraction name="ions:MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" id="Fact_57d6d4c6329f491692f3deb9abe73dc9" contextRef="c20240630_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction> million upfront payment, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_23a760b75190422bb42fa926fc6e5c35" contextRef="c20240630_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">485</ix:nonFraction> million in development and approval milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_cf9674ee7a4d40639845fc47a08f2971" contextRef="c20240630_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U002" decimals="-8" scale="9" format="ixt:num-dot-decimal">2.9</ix:nonFraction> billion in sales milestone payments. The agreement includes territory-specific development, commercial and medical affairs cost-sharing provisions. In addition, we are eligible to receive up
    to mid-<ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_0cbb7bc3d3724ea38eb75a8f5217fd43" contextRef="c20240101to20240630_RangeAxis_MinimumMember_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent royalties for sales in the U.S. and tiered royalties up to the high teens for sales outside the U.S.</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 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with ATTRv-PN. As a result, we began earning
    royalties from WAINUA sales, which we recognize as commercial revenue in our condensed consolidated statements of operations. We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_ace6b1f6af074e74a1fe02c606207a1f" contextRef="c20240630_RangeAxis_MinimumMember_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">30</ix:nonFraction> million upon regulatory approval of WAINUA for ATTRv-PN in the European Union, or EU, under this collaboration.</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 six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentage amounts):</div>
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          <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;">June 30,</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with AstraZeneca</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3c07696a556f4d42a344e4074f481996" contextRef="c20240401to20240630_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,960</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_320b45cd76504bdea07f87db95c3f2eb" contextRef="c20230401to20230630_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">59,501</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_204d7cdcf8c9448dbd7ceb724abc5850" contextRef="c20240101to20240630_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,645</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d8ff4a7ded664a499c467d436a9a469c" contextRef="c20230101to20230630_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">83,926</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_c427158a3b1049c29a458af6ce741328" contextRef="c20240401to20240630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">7</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_ec51c627416b40e6a246758dc5f84028" contextRef="c20230401to20230630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">32</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_9121973ebd8e47f793b80a4c27b76648" contextRef="c20240101to20240630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">8</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_699edd45e2b84dc7b47b3ce81f36c484" contextRef="c20230101to20230630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">26</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


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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 June 30, 2024 included deferred contract revenue of $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_3a20ada3cf094754aa60fe6a8bc997b3" contextRef="c20240630_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.9</ix:nonFraction> million from our relationship
    with AstraZeneca. We did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_71bd02ad16934a43a74cb215992392e1" contextRef="c20231231_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U002" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction>t have any deferred contract revenue from our relationship with AstraZeneca at December 31, 2023.</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. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. QALSODY, our medicine to treat patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS,
    received accelerated approval from the U.S. Food and Drug Administration, or FDA, in April 2023 and marketing authorization under exceptional circumstances from the European Medicines Agency, or EMA, in May 2024. In addition, we and Biogen are
    currently developing numerous other investigational medicines to treat neurodegenerative diseases, including medicines in development to treat people with amyotrophic lateral sclerosis, or ALS, SMA, Alzheimer&#8217;s disease, or AD, and Parkinson&#8217;s disease,
    or PD. 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 June 30, 2024, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_4de0101278b94f98a15dfb2c4990f91e" contextRef="c20240630_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-8" scale="9" format="ixt:num-dot-decimal">3.9</ix:nonFraction> billion in payments from our Biogen
    collaborations, including payments to purchase our stock.</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 2013 strategic neurology collaboration, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ff666cf26fde4ed99b7048e70b1c4032" contextRef="c20240401to20240630_ProductOrServiceAxis_QalsodyMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">20</ix:nonFraction> million milestone payment from Biogen when the EMA approved Biogen&#8217;s Marketing Authorization Application, or MAA, filing of QALSODY in the second quarter of 2024. We recognized this milestone
    payment as R&amp;D revenue in full in the second quarter of 2024 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next milestone payment for QALSODY of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_d334c9ec54f64e779d348fd8a5d1cef5" contextRef="c20240630_ProductOrServiceAxis_QalsodyMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">10</ix:nonFraction> million if the Ministry of Health, Labour and Welfare of Japan approves Biogen&#8217;s Japanese New Drug Application filing of QALSODY.</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 second quarter of 2024, Biogen's option to license ION582, an investigational antisense medicine for the potential treatment of
    Angelman Syndrome, expired unexercised. As a result, we recognized $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f9c95a391db949038f667544918461a2" contextRef="c20240401to20240630_ProductOrServiceAxis_Ion582Member_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">30</ix:nonFraction> million of R&amp;D revenue from previously deferred milestone payments
    related to the ION582 study because we did not have any remaining performance obligations. We will achieve the next milestone payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_47a0889dd6ca4e6bbad40aa94c1b19b6" contextRef="c20240630_ProductOrServiceAxis_IonisMaptMember_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction>
    million if Biogen advances IONIS-MAPT<sub>Rx</sub> into Phase 3 development under our 2012 neurology collaboration.</div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">12</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </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;">During the three and six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts):</div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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;">Revenue from our relationship with Biogen</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_8ebecbc9dc2f48c2b13f10faa30883df" contextRef="c20240401to20240630_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">138,159</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d2d9dc0a89f64bd9aedf1424e3725003" contextRef="c20230401to20230630_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">97,402</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0cb6a76328e84fdca0f3575ed46c7bb9" contextRef="c20240101to20240630_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">197,395</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0886e714596146329ef3aaa60e2c4ddc" contextRef="c20230101to20230630_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">167,903</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%;">
          <div style="text-align: left; text-indent: -8.9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_46a53177bab6411dbfa4bacef3eacf19" contextRef="c20240401to20240630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">61</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_3f7d76bc791847c7bd8e878596274ee8" contextRef="c20230401to20230630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">52</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_0f0eb4fc60434512b4407e359598effe" contextRef="c20240101to20240630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">57</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_c6510891f3034be2ab38f94f3553a832" contextRef="c20230101to20230630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">53</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
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  </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 condensed consolidated balance sheets at June 30, 2024 and December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>included deferred contract revenue of $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_06b0d8db296b4fe5923cb8d67d6c5f8a" contextRef="c20240630_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">241.8</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_9e226e0b46f94da29b560891abc17b11" contextRef="c20231231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">307.4</ix:nonFraction> million, respectively, from our relationship with Biogen.</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-style: italic; font-weight: bold;">Otsuka</div>
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<div><br/>
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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;">In 2023, we entered into an agreement with Otsuka
      Pharmaceutical Co., Ltd., or Otsuka, to commercialize donidalorsen in Europe. In the second quarter of 2024, we expanded the agreement to include commercialization rights for donidalorsen in the Asia-Pacific region in addition to Europe. As a result,
      we received a $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_6c655711f913424599f827b35b57967e" contextRef="c20240401to20240630_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">20</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment from Otsuka.
      Under the amended agreement, we are eligible to receive up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_5eb1d8c530464bce904ba3985f6340cd" contextRef="c20240630_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">290</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, which is comprised of $</span><ix:nonFraction name="ions:MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" id="Fact_128d8a5b3bd24f3fb34df87d960047ec" contextRef="c20240630_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">85</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in
      upfront payments, up to $</span><ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_ebff62fd21c543a186dcb074d0ccdac1" contextRef="c20240630_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">65</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestone
      payments and up to $</span><ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_90acf49a83794011806e00359abf03f6" contextRef="c20240630_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">140</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in sales milestone payments
      over the term of the collaboration. In addition, we are eligible to receive tiered royalties up to </span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_5eeaea3f1d6b460a99fee5797395cefa" contextRef="c20240101to20240630_RangeAxis_MaximumMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">30</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales. We are responsible for completing the ongoing development of donidalorsen. We retained the rights to commercialize donidalorsen in the U.S. and in the rest of the world, assuming
      regulatory approvals. </span>From inception through June 30, 2024, we have received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_9908223a724b43bbb5a7229b4e5a7adc" contextRef="c20240630_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">85</ix:nonFraction> million in payments from Otsuka.</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 identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_32f778391f4a4496af154c7cd48b779d" contextRef="c20240630_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> performance
    obligations under our amended agreement for the Asia-Pacific region, comprised of our license of donidalorsen to Otsuka and R&amp;D services for donidalorsen. We allocated the transaction price of $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_81d54cfaebd947deb6ab5d68fa1f55db" contextRef="c20240630_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">20</ix:nonFraction> million based on the estimated stand-alone selling price of each performance obligation as follows:</div>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_34cdea95c9c5489abcc178f49c251257" contextRef="c20240630_ProductOrServiceAxis_LicenseOfDonidalorsenMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">17.5</ix:nonFraction> million for the license of donidalorsen; and</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_032098637fee45519830704a2dfe5c4d" contextRef="c20240630_ProductOrServiceAxis_ResearchAndDevelopmentServicesForDonidalorsenMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.5</ix:nonFraction> million for the R&amp;D services for donidalorsen.</div>
        </td>

  </tr>


</table>
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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 the second quarter of 2024, we recognized $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f2042919e4f140d5ac3e5ebb12b59d25" contextRef="c20240401to20240630_ProductOrServiceAxis_LicenseOfDonidalorsenMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">17.5</ix:nonFraction>
    million as revenue in full because Otsuka had full use of the license without any continuing involvement from us. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our
    performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our R&amp;D services performance obligation in March 2026. We will achieve the next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_c8e58d1730f54a6481c1ada5c3bc10ef" contextRef="c20240630_ProductOrServiceAxis_DonidalorsenMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction> million if the EMA accepts a MAA filing for donidalorsen in the EU under this collaboration.</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;">During the three and six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amounts):</div>
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        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="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;">Revenue from our relationship with Otsuka</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b2d6f08d61154a86acb52afb84f317d9" contextRef="c20240101to20240630_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">19,691</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_2878e09042ef40cbb1c1569b7acb96e8" contextRef="c20230101to20230630_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_12a2c1c7a51a47d38c72934d5ef1241f" contextRef="c20240401to20240630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">8</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_6e372a373c3b44579f6596f4de23cc85" contextRef="c20230401to20230630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_1ec12f18de7d4d98aaff909bf2ea01c9" contextRef="c20240101to20240630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">6</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_cb63a8fc3d24488fb269ca16900573d4" contextRef="c20230101to20230630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


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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 sheets at June 30, 2024 and December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>included deferred contract revenue of $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_00aa3cf8e5724e7b92dc3f01615d5cbc" contextRef="c20240630_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.8</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_c8b7f42e789a48199eaaf038f1010919" contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.5</ix:nonFraction> million, respectively, from our relationship with Otsuka.</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_8708854e9f74489eaddb662a2a5a7aef" contextRef="c20240630_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> collaborations
    with Hoffmann-La Roche Inc. and F. Hoffmann-La Roche Ltd, collectively Roche: <ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_88ec4b34ccb1440fb83eddf3356dc9d8" contextRef="c20240630_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U008" 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&#8217;s disease, or HD, <ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_96da0a35ed7d49889330254361feb310" contextRef="c20240630_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U008" 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 immunoglobulin A, or IgA, nephropathy, or IgAN, and <ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_bbf576f22cda4aa1a7825d125b563a38" contextRef="c20240630_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> to develop RNA-targeted programs for AD and HD. From inception through June 30, 2024, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_f8214b3cc16a4ccd98a2eb8352c06a68" contextRef="c20240630_RangeAxis_MinimumMember_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">345</ix:nonFraction> million in payments from our Roche collaborations.</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 July 2024, Roche discontinued development</span> of
    IONIS-FB-L<sub>Rx</sub> for the treatment of geographic atrophy, or GA, following the completion of the Phase 2 study, which showed a favorable safety profile and target engagement, but insufficient efficacy to advance into Phase 3 development.</div>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">13</span></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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the IONIS-FB-L<sub>Rx</sub> collaboration for the treatment of IgAN, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_218eb9273609418bb87373608325b628" contextRef="c20240731_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">430</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_860714f8ce83469e9b8ff81c4caf2d1c" contextRef="c20240731_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction> million
    license fee, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_be59a0b2668848ecb101f706c150a2d5" contextRef="c20240731_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction> million in development milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_77f9d3e2c2534a859c60e0503d050567" contextRef="c20240731_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">90</ix:nonFraction> million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_b65d293159ac4b89adb7d1013f5ea184" contextRef="c20240731_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">280</ix:nonFraction> million in sales milestone
    payments. We will achieve the next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_7fe834140fcc4ba9a6767b3cb8f3bed9" contextRef="c20240731_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">23.5</ix:nonFraction> million if Roche advances IONIS-FB-L<sub>Rx</sub> for the treatment of IgAN under this
    collaboration.</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 six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Roche (in thousands, except percentage amounts):</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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  <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;">Revenue from our relationship with Roche</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <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>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_cbbf85f942984ba785e57736cc2b650e60" continuedAt="Text_cbbf85f942984ba785e57736cc2b650e61">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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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 condensed consolidated balance sheets at June 30, 2024 and December 31, 2023 included deferred contract revenue of $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_e844fd194db44bb8bbbd875009f2613d" contextRef="c20240630_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">15.0</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_98909439e129431f9e274be3996d9c23" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">36.7</ix:nonFraction> million, respectively,
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</ix:continuation></div>

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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6. Basic and Diluted Net Loss Per Share</div>
</ix:nonNumeric>

  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef3361" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef3362">
<div><br/>
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</ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef3362" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef3363"><ix:nonNumeric name="us-gaap:EarningsPerSharePolicyTextBlock" id="Text_9471c38bb7ae4e1287d0671ecea462a6" contextRef="c20240101to20240630" escape="true" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc04051">
<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;">Basic net loss per share</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef3363" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef3364"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc04051" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc04052">
<div><br/>
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef3364" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef3365"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc04052" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc04053">
<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 six months ended&#160;June 30, 2024 and 2023 by dividing our net loss by our weighted-average number of common shares outstanding during the period.</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef3365" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef3366"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc04053" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc04054">
<div><br/>
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef3366" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef3367"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc04054" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc04055">
<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;">Diluted net loss per share</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef3367" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef3368"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc04055" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc04056">
<div><br/>
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef3368" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef3369"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc04056" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc04057">
<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 six months ended&#160;June 30, 2024 and 2023, we incurred a net
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  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef3369" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef33610"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc04057" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc04058">
<div><br/>
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef33610" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef33611"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc04058" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc04059">
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef33611" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef33612"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc04059" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc040510">
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

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  </tr>


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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef33612" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef33613"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc040510" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc040511">
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

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  </tr>


</table>
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  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef33613" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef33614"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc040511" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc040512">
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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_e41939393b224ee783597306dc36daac" contextRef="c20230630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c5e88dec0bd1430ca7e7d1de977b5a01" contextRef="c20240630_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_a933b4f7afa1473d9df0d94a8d4afeb2" contextRef="c20230630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5fde4c84acc044728945d893da112927" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction>% Notes;</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef33614" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef33615"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc040512" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc040513">
<table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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_a93777dfde714e38820482b10cce8665" contextRef="c20230630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2ace2f3096e942c4bf2967102938f98f" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction>% Notes;</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef33615" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef33616"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc040513" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc040514">
<table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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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  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef33616" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef33617"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc040514" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc040515">
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef33617" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef33618"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc040515" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc040516">
<table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef33618" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef33619"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc040516" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc040517">
<table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
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  <ix:continuation id="Text_39a86af8510e4e5499cd4f2fac8ef33619" continuedAt="Text_39a86af8510e4e5499cd4f2fac8ef33620"><ix:continuation id="Text_b4069091aea84e5eb5a8b3f6babc040517" continuedAt="Text_b4069091aea84e5eb5a8b3f6babc040518">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
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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 June 30, 2024
    and 2023, we had warrants related to our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_79673f01eb3f4d0f8cc2a2ee82ba16a8" contextRef="c20240630_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_8b9684e867694bc788bcce48cf27b9cb" contextRef="c20240630_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>
</ix:continuation></ix:continuation></div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:InvestmentTextBlock" id="Text_9c14342eb23f428ab65b1e5fc1fe2953" contextRef="c20240101to20240630" escape="true" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a741">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7.&#160; Investments</div>
</ix:nonNumeric>

  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a741" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a742">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a742" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a743"><ix:nonNumeric name="us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock" id="Text_0fd547c923744c79bd4f06c68a515bf2" contextRef="c20240101to20240630" escape="true" continuedAt="Text_0aff641a16574cf7976d9dbc339097ec1">
<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 June 30, 2024:</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a743" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a744"><ix:continuation id="Text_0aff641a16574cf7976d9dbc339097ec1" continuedAt="Text_0aff641a16574cf7976d9dbc339097ec2">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a744" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a745"><ix:continuation id="Text_0aff641a16574cf7976d9dbc339097ec2">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; 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-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_4b3282e6abbf4694b90d56a12cb3a78d" contextRef="c20240101to20240630" format="ixt-sec:durwordsen">One year</ix:nonNumeric></span>
            or less</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" id="Fact_26a36804df4340729bec0b2f463acda4" contextRef="c20240630" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">75</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_3bd993e525784a5398b297b7856fe228" contextRef="c20240101to20240630" format="ixt-sec:durwordsen">one year</ix:nonNumeric></span>
            but within <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_beb1ea76eb4a4045aff26b90fc4a4ee3" contextRef="c20240101to20240630" format="ixt-sec:durwordsen">two years</ix:nonNumeric></span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" id="Fact_b3c2ee50dd694d208197df43360458a9" contextRef="c20240630" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">21</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; 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;">After <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_812c571149d64b329fe4410606d76c7a" contextRef="c20240101to20240630" format="ixt-sec:durwordsen">two years</ix:nonNumeric></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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" id="Fact_8cd01e7f5688446294ec6f1b2d7e38df" contextRef="c20240630" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">4</ix:nonFraction></div>
        </td>

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

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; 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</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" id="Fact_6217a171f5784696968b178278e97ffa" contextRef="c20240630" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a745" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a746">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a746" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a747">
<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 June 30, 2024,
    <ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" id="Fact_ecfa1cb8a4484b48a192e8436b1431fe" contextRef="c20240630" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">96</ix:nonFraction> percent of our available-for-sale securities had a maturity of less than <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_34c87d75876e42c988ffebc06f56b6a3" contextRef="c20240101to20240630" format="ixt-sec:durwordsen">two years</ix:nonNumeric>.</div>
</ix:continuation>
  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a747" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a748">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a748" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a749">
<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.</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a7410" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a7411">
<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 debt 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, Moody&#8217;s or Fitch, respectively.</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a7412" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a7413">
<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 June 30, 2024, we had an
    equity ownership interest of less than 20 percent in <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_b7edbc55e46842cb916a4ced56279788" contextRef="c20240630" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">seven</ix:nonFraction> private companies and <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_8144a98eb4174391a5f3065f3f804da4" contextRef="c20240630" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> public companies with which we conduct business.</div>
</ix:continuation>
  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a7413" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a7414">
<div><br/>
  </div>
</ix:continuation></div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">14</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </div>
<div><ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a7414" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a7415"><ix:nonNumeric name="us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock" id="Text_6d9fa3e82c0142dbb746fb5a3a6dc3c0" contextRef="c20240101to20240630" escape="true" continuedAt="Text_e72271f242ad41a3bb881d27ae1e5ebc1">
<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 (in thousands):</div>
</ix:nonNumeric></ix:continuation>

  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a7415" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a7416"><ix:continuation id="Text_e72271f242ad41a3bb881d27ae1e5ebc1" continuedAt="Text_e72271f242ad41a3bb881d27ae1e5ebc2">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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          <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;">June 30, 2024</span></div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#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 (1)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_7842515e18104a5cafcff84ddb01d951" contextRef="c20240630_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">552,837</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_6987932b0c734a95908cba3dde93f730" contextRef="c20240630_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,569</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_35d357c29e5b420daf82588703d78d8d" contextRef="c20240630_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">551,304</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_80e0d5c6be1c4870adc06685000bf257" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">121,781</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_18ba7ad7166c418da8278eb1c1894a6f" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_e9cc451da55c4d1c9aa3ad82c7ca9aae" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">310</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_9e8a5c54173d453cb9fb728033354336" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">121,476</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_17f5c15fd8fe452b890ee866cfaa6b85" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">650,997</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_45e8bcb24cc241f2bf8f293a9b67a6a6" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_36dcce36e9b446bcb8f2877352fd5851" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,105</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_cf007fb70961423eb9a3dd191872008b" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">649,904</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_7c05793868aa4afb94fcfb88fcffcb2b" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,083</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_6c641805a540462f9d84d76f2727c1e9" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">14</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_3e3856bd21754e01ab011686088d0aa5" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">42</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_893fcba0e0004d12b5940266add3822a" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,055</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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;">Total debt securities with a maturity of one year or less</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_3e165eb36915445a94e7bca3626be047" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,343,698</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_401ef7ec0ee84b33b734c6646f73945d" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,340,739</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Corporate debt securities</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_dff0a77ea162428eac31903b7ae1af1c" contextRef="c20240630_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">217,956</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 U.S. government agencies</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_4069992e62e44ec39ab5806e1ac879fa" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">115,349</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_13b8b3118986468c94cef784db3d7d85" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">72</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_8c034ba7ebd94e519637bf63e04e1b9f" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">317</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_907c5df34a09413bb109221fad1ea266" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">115,104</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_e43e28c5271b42a889a3b5a4967cc28d" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">127,240</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_4a47ab58cf674aa491198b0931ea7362" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_54bac431fed2433b9abbb4c98f4e8737" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,135</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_df46987f0ff442a68229243874a3a796" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">126,117</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_9945c8a3aa274e52aa7dfeabc6567ab4" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,668</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_2aa6d352ef954e92b94b3e1d7fb0194a" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_e6854048f6c941b08d43417760c49b8d" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">8</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_d4953054b98b42dba9d5bed9a4393226" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,660</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 debt securities with a maturity of more than one year</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_2b2ee63d727e423482b317c18a37ce81" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">462,896</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_22456af2bd1a42a5aaa84149b3a6373e" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">275</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_3f93907b739e4f8a80f71070bbbc98e2" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,334</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_33930b14001f46ccb9bf26b44f06a253" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">460,837</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale debt securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_c63efe923e13426992c34154ca0ceb66" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,806,594</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_4d9475d7048b443985ccf0e54c482dde" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">342</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_abe680e773e045d898d7e780327a8001" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,360</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_ed64a9779a3842959199d38607dc68f6" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,801,576</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;"><span style="text-decoration: underline;">Equity securities:</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Publicly traded equity securities included in other current assets (2)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_795298199a7149089987fd608d910788" contextRef="c20240630_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,897</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_95a1e63d6d4c49f48092f55cc7344a6f" contextRef="c20240630_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">334</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_720e14f204184668ac412128829c1d4c" contextRef="c20240630_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,377</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_c9668cdfca24444facba84f5586a8b21" contextRef="c20240630_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,854</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Privately held equity securities included in deposits and other assets (3)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_642c9681829a411280b706605512aec4" contextRef="c20240630_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">23,115</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_5465f26f407f4c8cbf1a7f4bc78d58bb" contextRef="c20240630_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,001</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_8f26e7f4482346919fb9fd971a0e1bd2" contextRef="c20240630_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,093</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_c86ece7c238c409db75f4e86d57eaa03" contextRef="c20240630_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">41,023</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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;">Total equity securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_74700e6175be499286aad7c1da529560" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">35,012</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_023010caa8f343509b0246de63732628" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,335</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_b4350186c9724e47b1cac8c01c4216b9" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,470</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_10dc545d20404abda7146b5a706c0e00" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">47,877</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px;">
          <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 debt and equity securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_6c45e37635ae4e82a8fe9a524ce7bc4f" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,841,606</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_5ab4e59a3fb946b2bfa63a42fd6cc9c5" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,677</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_571cea17cf8743fbb59b7749cbf08cd2" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,830</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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          <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, 2023</span></div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="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;">Corporate debt securities (1)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_b358568c049541b1856e64106205b629" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">559,967</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_870aab605dd4403c879855738490612a" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">157</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_e219351c2ba44027b99a7eb94f4fb4bd" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,625</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_baf860337cb14231b2612b277c5a61c8" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">557,499</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_68fdb285d5a54bedba4551932330f29f" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">224,711</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_90dbffe642224d96bbf19226414d77d9" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">64</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_1777d6b10a6444f78df8d692409a590a" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">611</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_2130cf6d51914dc0afd1eccb0e4dfdad" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">224,164</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_d8fc413c165c4a2c8aa4472257c08e29" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">513,784</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_c7bb5d4884cd42d0a8a8ff87cdcd691a" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">152</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_32a3a41f82bb44c799d99e85af07437d" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,889</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_4ed162913c2d4a49b2bae214aa82a90e" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">512,047</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_e6152f86899e46e196de685960cf0520" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,757</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_976e0d2fac214a4a8ce8d68be3812eda" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">42</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_e332742abab244fa8bc1de590d821dcc" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">113</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_072984a5e1e94320b84fd889d20ca860" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,686</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_5d62eb1de663460d8a9d559d81878a58" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,316,219</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_32d0c20dd09a4965be6545f5ef1e1d0e" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">415</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_a65f661f76de418c8ded0d80f7684b50" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,238</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_5269f1e3ba9b4b5f9397e201edccca32" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,311,396</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Corporate debt securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_a2fd30f9900b415194cd94d357af784b" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">243,151</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_34ab02ad304f441abe8a81962651c7ce" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,270</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_3d4b4abb3a29485786b07cbc63b828cb" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">692</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_e00dab3b4cb04062a2e6a17f853d0e52" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">243,729</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 U.S. government agencies</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_d714f0d4eecc4d92b9b830449bba7fd1" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">110,138</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_270ced43418a4c2faa9a7f0a3bd756eb" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">547</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_cc8c6fd4825a4a8ca13fdce32ea0a599" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">21</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_11b446490081470aa73bc2871b0b1042" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">110,664</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_e8d68ba6fad84cecafc9cdd32dea1e2f" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">294,873</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_28fa2a9aa6c3425bb5c7af4315f2d4c3" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,239</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_feb5ebb376f64b648a49adafb20944f7" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">480</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_5a7c49cad6044951b9d764adb62179ca" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">295,632</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_b4ec0071c45247e3b27a4b280e593780" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,466</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_31520233cfb642e0bb7685bb15133f3a" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_81b005a6831247d6a900198d8738b3d0" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_e281a6848521414491c86fcd9f85c8a9" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,469</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 debt securities with a maturity of more than one year</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_d8f9bd55d10c46e8a7923b828bf66f7b" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">651,628</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_9edb30f88d124e4f98e5fc6733baa317" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,063</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_35b1772ea2884933bfa48eab5441097a" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,197</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_bd78e79378ff4eecb24ada86ee7d4685" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">653,494</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale debt securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_d8842e093daf4aa8a441e191da86ea99" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,967,847</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_4a16a27e0c4144fea9d33948c111d40b" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,478</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_5d60bf6074c241728013af9aebe4f553" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,435</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_282a1da5440143508a579978a45d2601" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,964,890</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;"><span style="text-decoration: underline;">Equity securities:</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Publicly traded equity securities included in other current assets (2)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_b8a712e5f4af42cdb9018ff5937f5e79" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,897</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_8b35758c336d4c378e03fdeaeaa046d7" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">236</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_d23a46f787e04e259237398f99054fea" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,832</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_8651c4c7cf0b40ec9603b79cfd50d43b" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,301</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Privately held equity securities included in deposits and other assets (3)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_2faff3973c0f4ab0bd4fcffd3307bce8" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">23,115</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_e3dee8ea479d4e8fbda5e68ba7814a7e" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,001</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_53a829bbd230481e83c9e355f575a8b7" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,125</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_90b3f028c4c64df180eb902de39038aa" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">42,991</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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;">Total equity securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_cfbea931b88e4baf9112a7e54d02cbfc" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">35,012</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_5e7e8a83411f4b40bf00d16a3e60d487" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,237</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_d45ad7a12cac403ea2d5a2edb37a0eed" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,957</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_8bd47c89fd1645cfa78adda562a9364e" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,292</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px;">
          <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 debt and equity securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_6808aa03681547cca1d6c98d32aab031" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,002,859</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_f7a5c21d883b40c784a842b4eab86b9d" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,715</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_bf106be9d5824af3aa9e4c635557fb8a" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,392</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_ecad1868d9ae4c4cb68ebd3c78a85d30" contextRef="c20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,014,182</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
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  <tr>

    <td style="width: 18pt; vertical-align: top; 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 sheets.</ix:footnote></div>
        </td>

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</table>
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<div><br/>
  </div>
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    <td style="width: 18pt; vertical-align: top; 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 publicly traded equity securities are
            included in other current assets. We recognize publicly traded equity securities at fair value. In the six months ended&#160;June 30, 2024, we recorded a $<ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedGain" id="Fact_3313864190a543a6b47d32b6b504a1c9" contextRef="c20240101to20240630_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.6</ix:nonFraction>
            million net unrealized gain in our condensed consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies.</ix:footnote></div>
        </td>

  </tr>


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    <td style="width: 18pt; vertical-align: top; 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 privately held equity securities are included in deposits and other assets. We recognize our privately held 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, which are Level 3 inputs<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In the </span>six months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recorded a loss of $</span><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_a2833ea1ff084739bcc260fc19e5e29f" contextRef="c20240101to20240630_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.0</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in our condensed consolidated statements of operations related to changes in the
              fair value of our investments in privately held companies.</span></ix:footnote></div>
        </td>

  </tr>


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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">15</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </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 is a summary of our investments we consider to be temporarily impaired at June 30, 2024 (in thousands, except for number of investments):</div>
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="6">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="6">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="6">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%; 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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_333cdd7221c74a659058428cb96f027e" contextRef="c20240630_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U010" decimals="0" scale="0" format="ixt:num-dot-decimal">440</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_2e0cac4f3e6445e4af1d421cd8ba2264" contextRef="c20240630_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">517,394</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_903a58d3bf3c421b9166ac1d0a37f22d" contextRef="c20240630_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,155</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_183b7171ce6948fe93c1afb5708dc040" contextRef="c20240630_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">142,390</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_2bc4f2d4d6bd455e9474ce6348458023" contextRef="c20240630_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,288</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_6a521c4aea4b4d6186a40cc4ac11ef16" contextRef="c20240630_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,443</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_f82ef35b85bc4b76a2ca3ea408acca74" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U010" decimals="0" scale="0" format="ixt:num-dot-decimal">108</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_0a9f0760b76943a0bb457df5aa11d275" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">173,618</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_a606df5dbef24526ade176d96aa0c07b" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">482</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_2d0505e6d78b437083a13a36af9d0e35" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,892</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_be6630f1d422413eb69c31e0abbb4c84" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">145</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_9e4b0d43d3f14d11b3cdc492ef07dd02" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">199,510</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_eba3f72c498e466687adcba61f086b48" contextRef="c20240630_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">627</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_2e46b5062fb3478c908336d6d2d994c6" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U010" decimals="0" scale="0" format="ixt:num-dot-decimal">71</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_392a47ad8b314b019fde0f086884f91a" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">561,363</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_b473b5a2bf6f472895d5dbf195a86994" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">862</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_631f14e2221f4205b5b6af1f14754c3c" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">154,006</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_366adc85dd3e4261abd0ad4c81e9ed06" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,378</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_8fe8a8c8d9ba4dbe9a0815a2dd6c7215" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">715,369</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_039c758638b24f77831d5dfe6f4ab76e" contextRef="c20240630_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,240</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_2cef1dcb51a449edb7fe76af4b2c0e0c" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U010" decimals="0" scale="0" format="ixt:num-dot-decimal">45</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_2b2f7503adc14be999f6518218accc8a" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,449</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_f999f2e853164a178503a3147b33ac68" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">23</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_1ee53f584ab24cb6b581f7eae1eba196" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,319</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_98453b0c0b144bba86ec994206fdc1cb" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">27</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_4d01726992bb4d94b31e50877ad828f0" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,768</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_401d55f983434e8d9399ad8c2fc7758d" contextRef="c20240630_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">50</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <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; 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 temporarily impaired securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_a321ec73c6744478ab33de1911123ebf" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,260,824</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_32652639154d4153a0f3bf2d89e86160" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,522</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_c18b9c577f3c4038843a9b7ee496d0d4" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">331,607</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_b3760c7e65ef40e2ab47903dd7c9443a" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,838</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_08acbc6cc04049ed9b3d48be01027292" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,592,431</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_cf642061255f4432b68bd3618eb2a416" contextRef="c20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,360</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a7429" continuedAt="Text_d0362d76648c4d4d8d137cfbdda59a7430">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_d0362d76648c4d4d8d137cfbdda59a7430">
<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 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 intend to hold these securities
    to maturity and anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</div>
</ix:continuation></div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:FairValueDisclosuresTextBlock" id="Text_2a6de6f9bc2e421d838e9ff6c089fad5" contextRef="c20240101to20240630" escape="true" continuedAt="Text_93a2d0dc859d4b2f8f92c1555ac4efa81">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8.&#160; Fair Value Measurements</div>
</ix:nonNumeric>

  <ix:continuation id="Text_93a2d0dc859d4b2f8f92c1555ac4efa81" continuedAt="Text_93a2d0dc859d4b2f8f92c1555ac4efa82">
<div><br/>
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</ix:continuation>
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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 tables present the major security types we held at June 30, 2024 and December 31, 2023 that we regularly measure and carry at fair
    value. 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 security&#8217;s fair value (in thousands):</div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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;">June 30, 2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; 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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_ab8b93d31763462f825afbb8d94ca1c5" contextRef="c20240630_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">212,489</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_435272b4ab6d4fb0a17848af08d9ea64" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">212,489</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_b9e898ee93984d899874de0b216f6350" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_1b769ef466ea447fba9ad51918866940" contextRef="c20240630_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">769,260</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_1a622d10285342d4ab574fbc330e9b6a" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_2a11d5be65ff43b2bc3316d459599b2f" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">769,260</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; 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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_4ce9866198094ab9bb0fba527e9f7a46" contextRef="c20240630_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">236,580</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_cc73c7dd4336416d8872098ddc72f3db" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_418e9f44ebbb42dd9a510d3d5c448b72" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">236,580</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_80cb88c905824e2f9a4af8d421a3ae6c" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">776,021</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_2e48b747b93e49a19ff9c8c29a110e0c" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; 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 (3)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_c11eb07ea3324e24902d31be146e2aba" contextRef="c20240630_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">19,715</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_5239338c06b14e6a85429a23967f6b00" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_d3641150e44941fa942aa4dc4b80dcba" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">19,715</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <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 (4)</div>
          </div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_345ac2114958402e8c0526123b413533" contextRef="c20240630_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,854</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_49579a46ef144e9db6adc23b832e2254" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,854</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_714e6b6bc417487db0580f5a9df0b246" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_9623b6fc811d446d8de6fe8c0a84d07a" contextRef="c20240630_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,020,919</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_5e3adc88dc374a21be5199cc974a06ca" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">995,364</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_fb2ce086644c437499ac32ea8b2ab24d" contextRef="c20240630_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,025,555</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


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</ix:continuation></ix:continuation>
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<div><br/>
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_93a2d0dc859d4b2f8f92c1555ac4efa86" continuedAt="Text_93a2d0dc859d4b2f8f92c1555ac4efa87"><ix:continuation id="Text_9453db1a92f349f0b093e15d2dfd2a164" continuedAt="Text_9453db1a92f349f0b093e15d2dfd2a165">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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, 2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; 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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_3abef904d1ac4dac9365cd6a89ce306b" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">185,424</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_d7eb290d8c5b4341953ea8ce19b70167" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">185,424</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_9d277c8fc4ff4a19a7ee29dcea9663b9" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (5)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_6d98cfd31fed4be1bc5dd4e5765ff970" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">801,228</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_880b4c0e0d2d48df987d8eb4b3893eda" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_641d49c2d0c64af9adad977b14b03585" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">801,228</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; 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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_2c0dd2ce365841a7940c2b161ab7aa5b" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_276eb2ce23b74c76b7109fee3b729859" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">334,828</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_92f2c745baa2467ebc8da9f308582732" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">807,679</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_4f65ddc8bb1f41b18f4a4fafb05aa5bf" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">807,679</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_cad6d847f28b41d1ba345ee379c53c3a" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; 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 (3)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_8ac6126992144e2d902abafe0f05aaf1" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">21,155</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_c4b11390dafb4d68ab357a12be102e2b" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_984ae9d0003e4112b370b64ac08e73fa" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">21,155</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <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 (4)</div>
          </div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_2d42bf872f544c81919721ce64a97544" contextRef="c20231231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,301</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_e4b5ecb96353409f8174273ca47cf4bd" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,301</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_a7b2fd7148674fabb6e271a364c858e7" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_d3bd323a8b614ca5970873ceac15876b" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,156,615</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_309c74f6dec14486a89fc6b78983b26a" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">999,404</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_11ff54c661534a3abddbec83ad68c19a" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,157,211</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_93a2d0dc859d4b2f8f92c1555ac4efa87" continuedAt="Text_93a2d0dc859d4b2f8f92c1555ac4efa88"><ix:continuation id="Text_9453db1a92f349f0b093e15d2dfd2a165" continuedAt="Text_9453db1a92f349f0b093e15d2dfd2a166">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_93a2d0dc859d4b2f8f92c1555ac4efa88" continuedAt="Text_93a2d0dc859d4b2f8f92c1555ac4efa89"><ix:continuation id="Text_9453db1a92f349f0b093e15d2dfd2a166" continuedAt="Text_9453db1a92f349f0b093e15d2dfd2a167">
<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 sheets:</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_93a2d0dc859d4b2f8f92c1555ac4efa89" continuedAt="Text_93a2d0dc859d4b2f8f92c1555ac4efa810"><ix:continuation id="Text_9453db1a92f349f0b093e15d2dfd2a167" continuedAt="Text_9453db1a92f349f0b093e15d2dfd2a168">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_93a2d0dc859d4b2f8f92c1555ac4efa810" continuedAt="Text_93a2d0dc859d4b2f8f92c1555ac4efa811"><ix:continuation id="Text_9453db1a92f349f0b093e15d2dfd2a168" continuedAt="Text_9453db1a92f349f0b093e15d2dfd2a169">
<table cellspacing="0" cellpadding="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; 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.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_93a2d0dc859d4b2f8f92c1555ac4efa811" continuedAt="Text_93a2d0dc859d4b2f8f92c1555ac4efa812"><ix:continuation id="Text_9453db1a92f349f0b093e15d2dfd2a169" continuedAt="Text_9453db1a92f349f0b093e15d2dfd2a1610">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_93a2d0dc859d4b2f8f92c1555ac4efa812" continuedAt="Text_93a2d0dc859d4b2f8f92c1555ac4efa813"><ix:continuation id="Text_9453db1a92f349f0b093e15d2dfd2a1610" continuedAt="Text_9453db1a92f349f0b093e15d2dfd2a1611">
<table cellspacing="0" cellpadding="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; 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_2009e9e101cd4940acd892bb1ca9a15f" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_0a80d2918e1d4d1989dc35c373fb07fb" contextRef="c20240630_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">16.9</ix:nonFraction> million was included in cash and cash equivalents, with the difference included in short-term investments.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_93a2d0dc859d4b2f8f92c1555ac4efa813" continuedAt="Text_93a2d0dc859d4b2f8f92c1555ac4efa814"><ix:continuation id="Text_9453db1a92f349f0b093e15d2dfd2a1611" continuedAt="Text_9453db1a92f349f0b093e15d2dfd2a1612">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_93a2d0dc859d4b2f8f92c1555ac4efa814" continuedAt="Text_93a2d0dc859d4b2f8f92c1555ac4efa815"><ix:continuation id="Text_9453db1a92f349f0b093e15d2dfd2a1612" continuedAt="Text_9453db1a92f349f0b093e15d2dfd2a1613">
<table cellspacing="0" cellpadding="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; 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_67f6ff09f4d443248a7bd7fe03ce1bd9" 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_93a2d0dc859d4b2f8f92c1555ac4efa815" continuedAt="Text_93a2d0dc859d4b2f8f92c1555ac4efa816"><ix:continuation id="Text_9453db1a92f349f0b093e15d2dfd2a1613" continuedAt="Text_9453db1a92f349f0b093e15d2dfd2a1614">
<div><br/>
  </div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_ed9737c9dda047e8ac50c4c8ce6aa011" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in other current assets.</ix:footnote></div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_fa6fd00113af47ccbbac20179fb575e4" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_a08692d747714e4f965095878b94278d" contextRef="c20231231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">33.0</ix:nonFraction> million was included in cash and cash equivalents, with the difference included in short-term investments.</ix:footnote></div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">16</span></div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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;">Convertible Notes</div>
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<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_8d1f6865e68d404fba3a960ac202b794" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_651bad034a104e77bc2625750486ffb5" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction></ix:nonFraction>% Notes, <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_aaad9a13afbd4bdba290988f4527e23c" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b605dc05faaa4ecf92f3388ccd8e6140" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction>% Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_483e3008467a4a32945d0b38d6a65e03" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dfc304a4577d4a8b8ccf97e7be8f9791" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction>% Notes had a fair
    value of $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_6ec6de3fdf56419ca13cab79c9519015" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">634.4</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_e2d5869342504cbea6cdb10162937afd" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">649.6</ix:nonFraction>
    million and $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_886896b6a5b643a387fb328dcc366ca9" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">43.4</ix:nonFraction> million at June 30, 2024,
    respectively. Our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_30029ad2355341b4b3a2215eb70a0d89" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes, <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_75f72487616a426c92f2afcc07afe42b" contextRef="c20231231_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_fecc0db412a8437b9f266ba983d11303" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes had a fair value of $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_d42f5c070228490ba1f1f750e7d421f6" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">661.1</ix:nonFraction>
    million, $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_572d2a1ef8f740a6958da9503d2f0642" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">667.8</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_8ae98335d6764a84a41f7a8b186c6d75" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">42.4</ix:nonFraction>
    million at December 31, 2023, 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><ix:nonNumeric name="us-gaap:DisclosureOfCompensationRelatedCostsShareBasedPaymentsTextBlock" id="Text_68a9d92d88dc4032a19e261806b63702" contextRef="c20240101to20240630" escape="true" continuedAt="Text_ad9f981d6dd04d13965ebabadb9461e41">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">9. 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;">The following table summarizes stock-based compensation expense for the three and six months ended&#160;June 30, 2024 and 2023 (in thousands):</div>
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          <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;">June 30,</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" rowspan="1">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_8f8889793bc24130821266ebf7f8aedd" contextRef="c20240401to20240630_IncomeStatementLocationAxis_CostOfSalesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">246</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_192d34335f474b94af709bac4431ece0" contextRef="c20240101to20240630_IncomeStatementLocationAxis_CostOfSalesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">450</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_cc18bcac872c4daf934b3a3d0edf9b5a" contextRef="c20230101to20230630_IncomeStatementLocationAxis_CostOfSalesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">237</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <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;">Research, development and patent expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_03800ecd1ad747d0aba2047e92b6de26" contextRef="c20240401to20240630_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">22,766</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_9367ec0b16a34e4b94468ac1f96b68d2" contextRef="c20240101to20240630_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">44,991</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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  <tr>

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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stock-based compensation expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_cfcae472d24a41eba5315fc58eb907e1" contextRef="c20240101to20240630" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">62,068</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_ad9f981d6dd04d13965ebabadb9461e45" continuedAt="Text_ad9f981d6dd04d13965ebabadb9461e46">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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</ix:continuation>
  <ix:continuation id="Text_ad9f981d6dd04d13965ebabadb9461e46" continuedAt="Text_ad9f981d6dd04d13965ebabadb9461e47">
<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 June 30, 2024, 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="c20240630_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">61.6</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_221a3013ba19446cad9c335f9391fa1a" contextRef="c20240630_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">96.7</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_8257fd00a100452eab2bbbae92169ba5" contextRef="c20240630_AwardTypeAxis_PerformanceSharesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">13.8</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, including any PRSUs that do not vest. 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="c20240101to20240630_AwardTypeAxis_EmployeeStockOptionMember" format="ixt-sec:duryear">1.3</ix:nonNumeric> years, <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_94356ff2a4564b669110ba6365630dc9" contextRef="c20240101to20240630_AwardTypeAxis_RestrictedStockUnitsRSUMember" format="ixt-sec:duryear">1.6</ix:nonNumeric> years and <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_f9a42079a4f64b1699b01c5328b73f1f" contextRef="c20240101to20240630_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:duryear">1.9</ix:nonNumeric> years, respectively.</div>
</ix:continuation>
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<div><br/>
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</ix:continuation>
  <ix:continuation id="Text_ad9f981d6dd04d13965ebabadb9461e48" continuedAt="Text_ad9f981d6dd04d13965ebabadb9461e49">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Part IV, Item 15, 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, 2023 for further details on how we determine the fair value of stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP.</div>
</ix:continuation>
  <ix:continuation id="Text_ad9f981d6dd04d13965ebabadb9461e49" continuedAt="Text_ad9f981d6dd04d13965ebabadb9461e410">
<div><br/>
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</ix:continuation>
  <ix:continuation id="Text_ad9f981d6dd04d13965ebabadb9461e410" continuedAt="Text_ad9f981d6dd04d13965ebabadb9461e411">
<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 six months ended&#160;June 30, 2024 and 2023, we used the
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</ix:continuation>
  <ix:continuation id="Text_ad9f981d6dd04d13965ebabadb9461e411" continuedAt="Text_ad9f981d6dd04d13965ebabadb9461e412">
<div><br/>
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</ix:continuation>
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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>
</ix:nonNumeric></ix:continuation>
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        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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;">Risk-free interest rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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          <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: 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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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  </tr>

  <tr>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

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

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        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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;">Risk-free interest rate</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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          <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: 76%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_c44f5d5a2f164df58a55c39c846c87a6" contextRef="c20230101to20230630_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.0</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <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: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_bd9236668f60473db27e250b8060dc0d" contextRef="c20240101to20240630_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">38.4</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_b5d4da261dad4007b283535f0efbd4b2" contextRef="c20230101to20230630_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">36.7</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </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;">Expected life</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_4cc29778c0e447968d90cd4b1be3691e" contextRef="c20240101to20240630_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durmonth">6</ix:nonNumeric> months</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_6e6a732476bd479cad0b8af2fbcf4659" contextRef="c20230101to20230630_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durmonth">6</ix:nonNumeric> months</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_ad9f981d6dd04d13965ebabadb9461e417" continuedAt="Text_ad9f981d6dd04d13965ebabadb9461e418">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_ad9f981d6dd04d13965ebabadb9461e418" continuedAt="Text_ad9f981d6dd04d13965ebabadb9461e419">
<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;">RSUs:</div>
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<div><br/>
  </div>
</ix:continuation>
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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 weighted-average grant date fair value of RSUs granted to employees for the six months ended&#160;June 30, 2024 and 2023 was $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_7654fd0b1d374d55b0c76914d3cd1ad7" contextRef="c20240101to20240630_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">52.60</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_84da630fe5f54cd0a41a1019638d365c" contextRef="c20230101to20230630_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">39.50</ix:nonFraction> per share, respectively.</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation></div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">17</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </div>
<div><ix:continuation id="Text_ad9f981d6dd04d13965ebabadb9461e422" continuedAt="Text_ad9f981d6dd04d13965ebabadb9461e423">
<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;">PRSUs:</div>
</ix:continuation>

  <ix:continuation id="Text_ad9f981d6dd04d13965ebabadb9461e423" continuedAt="Text_ad9f981d6dd04d13965ebabadb9461e424">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_ad9f981d6dd04d13965ebabadb9461e424" continuedAt="Text_ad9f981d6dd04d13965ebabadb9461e425">
<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 terms of the PRSUs we granted in 2024 and 2023, <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_ee2c4be053bf4d4fa0f118c56e90ebdf" contextRef="c20240101to20240630_AwardDateAxis_GrantedIn2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_cbf3053ca8e544a2845e072c5fa5a23b" contextRef="c20240101to20240630_AwardDateAxis_GrantedIn2024Member_AwardTypeAxis_PerformanceSharesMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction></ix:nonFraction> percent of the PRSUs may vest at the end of the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_9b5887d1a570488aacfe20f1184224d2" contextRef="c20240101to20240630_AwardDateAxis_GrantedIn2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" format="ixt-sec:durwordsen"><ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_ae9ec08f58e1428b8e5cb44dcf0f4b8f" contextRef="c20240101to20240630_AwardDateAxis_GrantedIn2024Member_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric></ix:nonNumeric> performance period
    based on our relative TSR as compared to a peer group of companies and as measured at the end of the performance period. Under the terms of the grants, <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" id="Fact_9adf31a81b37424ba5ceceeb2b680336" contextRef="c20240101to20240630_AwardDateAxis_GrantedIn2024Member_AwardTypeAxis_PerformanceSharesMember" unitRef="U001" decimals="INF" scale="0" format="ixt-sec:numwordsen"><ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" id="Fact_29b835c3ddfd4dc5ab1566473b632e77" contextRef="c20240101to20240630_AwardDateAxis_GrantedIn2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U001" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction></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_ff7ab7a487cb4ba0a0e92defee6b71c3" contextRef="c20240101to20240630_AwardDateAxis_GrantedIn2024Member_AwardTypeAxis_PerformanceSharesMember_RangeAxis_MinimumMember" unitRef="U003" decimals="INF" scale="0" format="ixt-sec:numwordsen"><ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_211159fa772f42fe85db7b075cbfbbec" contextRef="c20240101to20240630_AwardDateAxis_GrantedIn2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MinimumMember" unitRef="U003" decimals="INF" scale="0" format="ixt-sec:numwordsen">zero</ix:nonFraction></ix:nonFraction>
    to <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_0e7b60fe29aa482d8859dbb9cc4cfdf9" contextRef="c20240101to20240630_AwardDateAxis_GrantedIn2024Member_AwardTypeAxis_PerformanceSharesMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_0d3c47a0216c47e79e969763111e120c" contextRef="c20240101to20240630_AwardDateAxis_GrantedIn2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">200</ix:nonFraction></ix:nonFraction> percent of the target number depending on our relative TSR.</div>
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<div><br/>
  </div>
</ix:continuation>
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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 weighted-average grant date fair value of PRSUs we granted to our executive officers for the six months ended&#160;June 30, 2024 and 2023 was $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_ef4bc03bc66841889f6c887d0636e91f" contextRef="c20240101to20240630_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">78.41</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_f37b71af46f844b7971b1a2b89993315" contextRef="c20230101to20230630_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">58.99</ix:nonFraction> per share, respectively.</div>
</ix:continuation></div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:IncomeTaxDisclosureTextBlock" id="Text_d3ef5f132e9f4b459c8640b25e10b2da" contextRef="c20240101to20240630" escape="true" continuedAt="Text_01739a4e41e34b099e7d3998f6ebee761">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -45pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">10.&#160; Income Taxes</div>
</ix:nonNumeric>

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<div><br/>
  </div>
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  <ix:continuation id="Text_01739a4e41e34b099e7d3998f6ebee762" continuedAt="Text_01739a4e41e34b099e7d3998f6ebee763">
<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 income tax expense of $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_db04407755a448ca8c0477393e35da6a" contextRef="c20240401to20240630" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction>
    million and $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_1d0e4d1794fd4e4da3a23adcf357d8a0" contextRef="c20240101to20240630" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction> million for the three and six months ended&#160;June 30, 2024, respectively, compared to $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_1302d10328b04b8e9fc43163f1371d1d" contextRef="c20230401to20230630" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.8</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_64064152ef0649a6be135594bdee86b8" contextRef="c20230101to20230630" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">19.2</ix:nonFraction> million for the same periods in 2023, respectively. The decrease in income tax expense relates primarily to the impact of the royalty purchase agreement with Royalty Pharma on income tax
    expense for the three and six months ended&#160;June 30, 2023. We reflected the Royalty Pharma transaction as a taxable sale, which required us to include the proceeds from the sale, net of currently deductible issuance costs, as taxable income in 2023.</div>
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<div><br/>
  </div>
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  <ix:continuation id="Text_01739a4e41e34b099e7d3998f6ebee764">
<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 continue to maintain a full valuation allowance on all our net deferred tax assets.</div>
</ix:continuation></div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:OtherLiabilitiesDisclosureTextBlock" id="Text_f2a697cc2a48421a914d3e69877cc71e" contextRef="c20240101to20240630" escape="true" continuedAt="Text_45d6d5149c004f05903e65395e168fcc1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">11. Liability Related to Sale of Future Royalties</div>
</ix:nonNumeric>

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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;">In January 2023, we entered into a royalty purchase agreement with Royalty Pharma to monetize a portion of our future SPINRAZA and
    pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. As a result, we received an upfront payment of $<ix:nonFraction name="ions:UpfrontRoyaltyPaymentReceived" id="Fact_378c023c31584e55b0617bdf49309947" contextRef="c20230101to20230131_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">500</ix:nonFraction>
    million and we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForAdditionalMilestones" id="Fact_45c4a4d71b5f46aa8fc6a9fd8e84328e" contextRef="c20240630_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">625</ix:nonFraction> million in additional milestone payments. Under the terms of the agreement, Royalty Pharma will
    receive <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_01f145be530749a2b5f41c92469f3150" contextRef="c20240630_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_4defe32cd3804cbb97e4c7a2e3a297be" contextRef="c20240630_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">45</ix:nonFraction> percent of royalty payments in 2028, on up to $<ix:nonFraction name="ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" id="Fact_4af0123d3f9a49d28566cdb7b703162e" contextRef="c20240630_ProductOrServiceAxis_SpinrazaMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.5</ix:nonFraction> billion in annual sales. In
    addition, Royalty Pharma will receive <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_5ab159c91cd6498eabdc7aec74f5b116" contextRef="c20240630_ProductOrServiceAxis_PelacarsenMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of any future royalty payments on pelacarsen, our medicine in development to treat patients
    with elevated lipoprotein(a)-driven cardiovascular disease. Royalty Pharma&#8217;s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $<ix:nonFraction name="ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" id="Fact_8efbfdbd4aec4c57ba48a38ed1338a40" contextRef="c20240630_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">475</ix:nonFraction> million or $<ix:nonFraction name="ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" id="Fact_d8115145c7914c85b8aa1e8af6fd697a" contextRef="c20240630_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">550</ix:nonFraction> million, depending on the timing and occurrence of FDA approval of
    pelacarsen.</div>
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<div><br/>
  </div>
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  <ix:continuation id="Text_45d6d5149c004f05903e65395e168fcc4" continuedAt="Text_45d6d5149c004f05903e65395e168fcc5">
<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 upfront payment of $<ix:nonFraction name="ions:UpfrontRoyaltyPaymentReceived" id="Fact_9289646b66ea4d879d32f2749df14834" contextRef="c20230101to20230131_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">500</ix:nonFraction>
    million as a liability related to the sale of future royalties, net of transaction costs of $<ix:nonFraction name="ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_0d96a5f873d84c6c9e556c6b4c988070" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.4</ix:nonFraction> million, which we are amortizing over the
    estimated life of the arrangement using the effective interest rate method. We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We record royalty payments made to Royalty
    Pharma as a reduction of the liability.</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation>
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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 the effective interest rate used to record interest expense under this agreement based on an estimate of future royalty
    payments to Royalty Pharma. As of June 30, 2024, the estimated effective interest rate under the agreement was <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_b086ad26f3df4c96a5fb5a381fd3f7e6" contextRef="c20240630_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">13.5</ix:nonFraction> percent.</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_45d6d5149c004f05903e65395e168fcc8" continuedAt="Text_45d6d5149c004f05903e65395e168fcc9"><ix:nonNumeric name="us-gaap:OtherNoncurrentLiabilitiesTableTextBlock" id="Text_96e6cdff125b48ec820d34ebadba6671" contextRef="c20240101to20240630" escape="true" continuedAt="Text_733a19c66b634769a7b920815fbbe4131">
<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 sets forth information on our liability related to sale of future royalties
    (in thousands):</div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_45d6d5149c004f05903e65395e168fcc10" continuedAt="Text_45d6d5149c004f05903e65395e168fcc11"><ix:continuation id="Text_733a19c66b634769a7b920815fbbe4132">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <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;">Proceeds from sale of future royalties in January 2023</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ProceedsFromSaleOfFutureRoyalties" id="Fact_43ce69c69d2e4a9f981a2bd01cf03a45" contextRef="c20230101to20230131_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">500,000</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Issuance costs related to sale of future royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_72f284990c0f4d5eaa9acbc3d2493707" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,434</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </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;">Royalty payments to Royalty Pharma</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:RoyaltyPayments" id="Fact_8ae2ba857c9b4817b07e3f9a9503ba12" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">44,628</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </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;">Interest expense related to sale of future royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:InterestExpenseRelatedToSaleOfFutureRoyalties" id="Fact_2a5f792f09cd4fbcbd0efc16a57bb504" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">68,238</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_dbf1a3a7ce1b4932b155049240c94a4a" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">560</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Net liability related to sale of future royalties as of December 31, 2023</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet" id="Fact_886a4872d05440beac01bb5287b39251" contextRef="c20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">513,736</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Royalty payments to Royalty Pharma</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:RoyaltyPayments" id="Fact_507f8204b5a0488eaa3f8e7285488644" contextRef="c20240101to20240630_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,236</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </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;">Interest expense related to sale of future royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:InterestExpenseRelatedToSaleOfFutureRoyalties" id="Fact_7f1f33033ed048b5b01a9e5613dea9ce" contextRef="c20240101to20240630_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">35,949</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_04391b8b969944e9b5fb4ee32f9f9b92" contextRef="c20240101to20240630_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">305</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; padding-bottom: 4px;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net liability related to sale of future royalties as of June 30, 2024</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet" id="Fact_3b7b9d43c6f54a7cacb07fc1a05bb2bc" contextRef="c20240630_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">533,754</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
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  <ix:continuation id="Text_45d6d5149c004f05903e65395e168fcc12">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of royalty
    payments from Biogen and Novartis, and result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the commercial sales of SPINRAZA, the regulatory approval and commercial sales of
    pelacarsen, competing products or other significant events. </div>
</ix:continuation></div>

  <div><br/>
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">18</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </div>
<div><ix:nonNumeric name="us-gaap:DebtDisclosureTextBlock" id="Text_932c025cb1a047c69adb81a74fc1d444" contextRef="c20240101to20240630" escape="true" continuedAt="Text_560a7452844745949e4f26de963c9cba1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">12. Convertible Debt</div>
</ix:nonNumeric>

  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba1" continuedAt="Text_560a7452844745949e4f26de963c9cba2">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba2" continuedAt="Text_560a7452844745949e4f26de963c9cba3">
<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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8fd7985775c44bfcace9d8ce7112cfeb" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction> Percent
    Convertible Senior Notes</div>
</ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba3" continuedAt="Text_560a7452844745949e4f26de963c9cba4">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba4" continuedAt="Text_560a7452844745949e4f26de963c9cba5">
<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 2023, we completed a $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_9ac73a0c76054664989ce3b276636b04" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">575.0</ix:nonFraction>
    million offering of convertible senior notes and used $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_e65b7027573d4d0fa002f8db903ff534" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">488.2</ix:nonFraction> million of the net proceeds from the issuance of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_406d1a1bdf0b4ba1876e7c87768507dd" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes to repurchase $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_6adbda144ad541519a85f04742f7fe37" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">504.4</ix:nonFraction> million in
    principal of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_aa260fe8f27f4107b319ed5903eeeac9" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes. We expect to use the remaining net proceeds to settle the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c43b19935fcd4795b1b3242bab81b367" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes that remain outstanding and for general corporate and working capital purposes.</div>
</ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba5" continuedAt="Text_560a7452844745949e4f26de963c9cba6">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba6" continuedAt="Text_560a7452844745949e4f26de963c9cba7"><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_a6052bc8837240ebaade9f70205e7cda" contextRef="c20240101to20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" escape="true" continuedAt="Text_9bb44fffa3b7475cb224660683db3b9d1">
<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 June 30, 2024, we had the following
    <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1d9824693ca647f4b8493a97101ddfc4" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes outstanding (in millions except interest rate and price per share data):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba7" continuedAt="Text_560a7452844745949e4f26de963c9cba8"><ix:continuation id="Text_9bb44fffa3b7475cb224660683db3b9d1" continuedAt="Text_9bb44fffa3b7475cb224660683db3b9d2">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba8" continuedAt="Text_560a7452844745949e4f26de963c9cba9"><ix:continuation id="Text_9bb44fffa3b7475cb224660683db3b9d2">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_493083a106b640dfb30fc2df3363ada0" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_16f4cefcf3bb4178bd27236563ff3ff8" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">575.0</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredFinanceCostsNet" id="Fact_cc60571356a14f7986c00ab61560a9dc" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U002" decimals="-5" scale="6">11.4</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_ac460e99cb6b43a8b64e987880ed0dd5">June 2028</span></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Interest rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_427672d827e5468ca1aa478fe963dfd0" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </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;">Effective interest rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_9a8e690230834f42858d17acc18433f0" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">2.3</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_2508d5a342a249ecbe2d658f907d3a63" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U004" decimals="2">53.73</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Total shares of common stock subject to conversion</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleSharesSubjectToConversion" id="Fact_bfa13a09b4f34edabb1b3a7da10b5d07" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.7</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba9" continuedAt="Text_560a7452844745949e4f26de963c9cba10">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba10" continuedAt="Text_560a7452844745949e4f26de963c9cba11">
<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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_0e3676949d7c473e97d1d20974f8f44c" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction> Percent
    Convertible Senior Notes and Call Spread</div>
</ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba11" continuedAt="Text_560a7452844745949e4f26de963c9cba12">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba12" continuedAt="Text_560a7452844745949e4f26de963c9cba13"><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_74f2863953cd4c8a92fbe46c683ba95f" contextRef="c20240101to20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" escape="true" continuedAt="Text_411b9548aa58413c9b84a436a847c7251">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At June 30, 2024, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_16e7fa8c1a5840b1ac5c8aa87a6ecf14" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes outstanding (in millions except interest rate and price
    per share data):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba13" continuedAt="Text_560a7452844745949e4f26de963c9cba14"><ix:continuation id="Text_411b9548aa58413c9b84a436a847c7251" continuedAt="Text_411b9548aa58413c9b84a436a847c7252">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba14" continuedAt="Text_560a7452844745949e4f26de963c9cba15"><ix:continuation id="Text_411b9548aa58413c9b84a436a847c7252">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_72099b84515a4987a6ed39e66479bffc" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_a67ad95abe2d4dd9908f49e9f2b5ff38" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">632.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredFinanceCostsNet" id="Fact_5ec7acd6c2514e8cabe31debb2a3b6a9" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_edbb9fb31e834f86ad026d22e567df04">April 2026</span></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Interest rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_eb33a4a1dda248649a730b726ee6e4ab" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </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;">Effective interest rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_63a78b08d33541519708442f3d1e2957" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_95d4f72d952f49fb80b34fdc489ad77a" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">57.84</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_81a2de43ec8947979830016c7ae89c30" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">76.39</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleSharesSubjectToConversion" id="Fact_88ccdeff6aeb43b2b0d735cbf3651c87" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.9</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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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>
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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 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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8d1a4d03d8144e47b63f8e4fe5edea5e" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes by increasing the effective conversion price on our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f647ae8c9e9d49c78dd3b8a8f601fbe6" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes. We increased our effective conversion price to $<ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_8f89399b6ebc43edbd9bf57eae0f6a00" contextRef="c20240630_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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e1f0bf581c4e4cd09ceef3c4a8c66d8b" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%&#160;</span>Notes.
    The call spread cost us $<ix:nonFraction name="ions:CallSpread" id="Fact_adc134900f3e4b2a8095bb94c51ff448" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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_27fba3d5bc6e4961a0ec541d9ce880e5" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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_fae589c1422f409bab0ef5a3d362a9d2" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f275e8ed60f84ce58a3fb217a7effde2" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes, our note hedges are subject to adjustment. Additionally, our note hedges
    are exercisable upon conversion of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9a0025dc07b948759f15259d7f5c6fdb" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes. The note
    hedges will expire upon maturity of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_26151b0f7f634b91a20e7b74ac5f57d7" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes, or April
    2026. The note hedges and warrants are separate transactions and are not part of the terms of our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7bd39b60327b4b2a961691b5ae863d0a" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes. The holders of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c3580cc62da242428fa842ae2cebc7fc" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes do not have any rights with respect to the note hedges and warrants.</div>
</ix:continuation>
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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;">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 sheets. Refer to Part IV, Item 15, 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, 2023 for our Call Spread accounting policy. 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><br/>
  </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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a33ce35bdd374749b6f33e880968b6c9" contextRef="c20240630_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><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;">As discussed above, in 2023, we repurchased $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_2a8aa299b11243dc8e7e302b9855032f" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">504.4</ix:nonFraction>
    million of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9f7f690d52f945a49bfbdce14f334871" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes.</div>
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<div><br/>
  </div>
</ix:continuation></div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">19</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </div>
<div><ix:continuation id="Text_560a7452844745949e4f26de963c9cba24" continuedAt="Text_560a7452844745949e4f26de963c9cba25"><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_4533b9a35aa54a2d981119b07e67d99c" contextRef="c20240101to20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" escape="true" continuedAt="Text_0cc978ac83624ae2a318dd168644dfcc1">
<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 June 30, 2024, we had the following
    <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c91fd8cfcca146eeaee60bbae9843a5c" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes outstanding with interest payable semi-annually (in millions except interest rate and price per share data):</div>
</ix:nonNumeric></ix:continuation>

  <ix:continuation id="Text_560a7452844745949e4f26de963c9cba25" continuedAt="Text_560a7452844745949e4f26de963c9cba26"><ix:continuation id="Text_0cc978ac83624ae2a318dd168644dfcc1" continuedAt="Text_0cc978ac83624ae2a318dd168644dfcc2">
<div><br/>
  </div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c74c7559f3794aff8fd34e6e71dc7e36" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_8fdb29e27b1249be96c416b7e1afbe6f" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">44.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredFinanceCostsNet" id="Fact_ef8abebcb9cd4d2c8d22e438aa20d596" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_9ad2e8b4fef74d3cab598aa38f5df4fd">December 2024</span></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Interest rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5f715031591b4fe6a0024076fc0b6dae" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </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;">Effective interest rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_4a8586e56b5f42e494ac20b9ebaf16ba" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_cd9641bba27d48d89431b73d453aae5e" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">83.28</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_4825eb43f8064051b13d428922900c94" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">123.38</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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, excluding shares related to <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_701801bad83c4feb95778b3887b39a59" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></span>% Notes that we have repurchased and are currently holding in treasury</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleSharesSubjectToConversion" id="Fact_1a6966cb93514cde8fc57a63185f51f0" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </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 conjunction with the issuance of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c6a7865d9b5b492081a7f522b07e11fa" contextRef="c20240630_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 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_866d978c915841dea195724419fef4e3" contextRef="c20240630_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_14b15285e173484ebef7a46abc2036df" contextRef="c20240630_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_29947f32d3ab4719a35411e18b063bb2" contextRef="c20240630_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_12dd621b8581486fae2021f59964df1e" contextRef="c20240630_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_aa24cd7f5c614512b1647e86a78f4031" contextRef="c20190101to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" 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_f3981ee582ef4443af493f8da7ca2b64" contextRef="c20190101to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" 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_66c802772ac04d93a9ee2afafef489b6" contextRef="c20190101to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" 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_114816fa082a426dba291250c81fb6a1" contextRef="c20240630_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_f94762bb86964ced9cbdb14a7295aad0" contextRef="c20240630_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_b48f6a51f5c64b7e8214ed3445df6131" contextRef="c20240630_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_b72359aeedb54807b8b03fc26f0a7bfa" contextRef="c20240630_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_4e836a7f0c1d4f8ca2688d3e4a6dfede" contextRef="c20240630_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. As of </span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the note hedges and warrants remain outstanding.</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 sheets. 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-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_ab48834238d94f4fa9c36835a1893833" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2e4a8b6cc00b43f29c990216f40a4bb7" contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%
      and </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8339e5213d28400e84342b3e1d73f657" contextRef="c20240630_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_24a1472dd1fd427ebaeb793afee4e0ab" contextRef="c20240101to20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_a38abeae4ec74a3eaf19e2d07a941668" contextRef="c20240101to20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_229a2def62c24eed980d9982856538b0" contextRef="c20240101to20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction></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></div>
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  <div><br/>
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<div><ix:nonNumeric name="us-gaap:LegalMattersAndContingenciesTextBlock" id="Text_00889d79158c44ab9838be43f7bac562" contextRef="c20240101to20240630" escape="true" continuedAt="Text_ca9073352c184df89c684cc88b852a361">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">13. 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are no pending material legal proceedings to which we are a party or of which our property is the subject.</div>
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

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    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 2.</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-weight: bold;">MANAGEMENT&#8217;S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS</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; 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>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Forward-Looking Statements</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;">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 our commercial medicines, additional medicines in development and technologies. 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 and particularly 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, 2023, 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. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="OverviewQ2"><!--Anchor--></a>Overview</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For three decades as a pioneer in RNA-targeted medicines, we have focused on bringing better futures to people with serious diseases.
    Today, we continue to drive innovation in RNA therapies. A deep understanding of disease biology and an industry-leading drug discovery technology propels our work, coupled with a passion and urgency to deliver better futures for patients.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We currently have five marketed medicines to treat serious diseases: SPINRAZA (nusinersen), QALSODY (tofersen), WAINUA (eplontersen),
    TEGSEDI (inotersen) and WAYLIVRA (volanesorsen). We also have a rich innovative late- and mid-stage pipeline in neurology, cardiology and other areas of high patient need. We currently have nine medicines in Phase 3 development and multiple additional
    medicines in early and mid-stage development.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are using our multiple sources of revenue and our capital structure to continue investing in our commercial readiness efforts for
    multiple late-stage programs, our innovative pipeline and our technology. By continuing to focus on these priorities, we believe we are well positioned to drive future growth and to bring next-level value to patients and shareholders.</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;">Marketed Medicines</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;">SPINRAZA is an antisense medicine for the treatment of
      patients with spinal muscular atrophy, or SMA, a progressive, debilitating and often fatal genetic disease. Our partner, Biogen, is responsible for commercializing SPINRAZA worldwide</span>. From inception through June 30, 2024, we have earned more than $2.2
    billion in revenues from our SPINRAZA collaboration, including more than $1.7 billion in royalties on sales of SPINRAZA.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">QALSODY is an antisense medicine that received accelerated approval from the United States, or U.S., Food and Drug Administration, or FDA,
    in April 2023 and marketing authorization under exceptional circumstances from the European Medicines Agency, or EMA, in May 2024 for the treatment of adult patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS, a rare,
    neurodegenerative disorder that causes progressive loss of motor neurons leading to death. Our partner, Biogen, is responsible for commercializing QALSODY worldwide.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA is a once monthly, self-administered subcutaneous LIgand-Conjugated Antisense, or LICA, medicine that received approval from the
    FDA in December 2023 and Health Canada in June 2024 for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis, or ATTRv-PN, a debilitating, progressive, and fatal disease. WAINUA is the only approved medicine for
    the treatment of ATTRv-PN that can be self-administered via an auto-injector. We and AstraZeneca are commercializing WAINUA in the U.S. with the launch having commenced in January 2024. We and AstraZeneca are seeking regulatory approval for WAINUA in
    Europe and other parts of the world. AstraZeneca has exclusive rights to commercialize WAINUA outside of the U.S.</div>

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    </div>

  </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 ATTRv-PN. We sell TEGSEDI in the U.S. and Canada (collectively, North America) and Europe through our distribution agreement with Swedish Orphan Biovitrum AB, or Sobi. In October 2023, our agreement for TEGSEDI in North America was
    terminated. As a result, Sobi is transitioning responsibilities to us. In February 2024, we began the process to withdraw the TEGSEDI New Drug Application, or NDA. In Latin America, PTC Therapeutics International Limited, or PTC, is commercializing
    TEGSEDI in Brazil and is pursuing access in additional Latin American countries through its exclusive license agreement with us.</div>

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  </div>

  <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 approved in Europe and Brazil as an adjunct to diet in adult patients
    with genetically confirmed familial chylomicronemia syndrome, or FCS, and at high risk for pancreatitis. We sell WAYLIVRA in Europe through our distribution agreement with Sobi. In Latin America, PTC is commercializing WAYLIVRA in Brazil for two
    indications, FCS and familial partial lipodystrophy, or FPL, and is pursuing access in additional Latin American countries through its exclusive license agreement with us.</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;">Medicines in Registration and Phase 3 Studies</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We currently have nine medicines in registration or Phase 3 studies for eleven indications, which are:</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA is our medicine to treat patients with transthyretin amyloidosis, or ATTR, that is approved in the U.S. and Canada for the
    treatment of adults with ATTRv-PN, under regulatory review in other countries for ATTRv-PN and in development for ATTR cardiomyopathy, or ATTR-CM. In January 2024, we launched WAINUA for the treatment of adults with ATTRv-PN in the U.S. In September
    2023, The <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Journal of the American Medical Association</span>, or <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">JAMA</span>, published positive results from the Phase 3 NEURO-TTRansform study in patients with ATTRv-PN showing WAINUA halted disease progression and continuously improved quality of life at the 35-, 66- and 85-week analyses. In July 2023,
    we completed enrollment of the Phase 3 CARDIO-TTRansform study of WAINUA in patients with ATTR-CM with data expected in 2026. In February 2024, the FDA granted Fast Track designation to WAINUA for the treatment of patients with ATTR-CM. Additionally,
    in January 2022 and October 2023, the FDA and EMA, respectively, granted Orphan Drug designation to WAINUA for the treatment of ATTR. In June 2024, Health Canada approved WAINUA for the treatment of adults with ATTRv-PN.</div>

  <div><br/>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Olezarsen is our medicine in development for FCS, an ultra-rare indication and severe hypertriglyceridemia, or sHTG, a much broader
    indication. In June 2024, the FDA accepted our NDA for patients with FCS for Priority Review with a Prescription Drug User Fee Act, or PDUFA, date of December 19, 2024. In April 2024, we presented positive data from the Phase 3 Balance study in
    patients with FCS and the Phase 2b Bridge study in patients with HTG and sHTG at the American Academy of Cardiology meeting with simultaneous publications in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">New England Journal of Medicine</span>, or <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">NEJM</span>. Additionally, in April 2024, we opened our Expanded Access Program for patients with
    FCS in the U.S.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">&#160;</span>In September 2023, we reported positive results from the Phase 3 Balance study in patients with FCS showing statistically
    significant triglyceride lowering and a substantial reduction in acute pancreatitis events in addition to a favorable safety and tolerability profile. Additionally, we are currently conducting a broad Phase 3 development program for olezarsen for the
    treatment of sHTG including three Phase 3 studies supporting development (CORE, CORE2 and ESSENCE), which achieved full enrollment in 2024. The FDA granted Breakthrough Therapy designation, Orphan Drug designation and Fast Track designation to
    olezarsen for the treatment of FCS.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Donidalorsen is our medicine in development for hereditary angioedema, or HAE. In May 2024, we presented positive data from the Phase 3
    OASIS-HAE study in patients treated every four weeks and every eight weeks. In addition, we presented positive data from OASISplus, our trial that includes an open-label, or OLE, cohort for patients rolling over from the Phase 3 study and a separate
    cohort for patients who have transitioned to donidalorsen from other prophylactic HAE medications that we refer to as the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8220;</span>switch study,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8221;</span> with simultaneous publications in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">NEJM</span>. In December 2023 and June 2024, we licensed
    commercialization rights for donidalorsen to Otsuka Pharmaceutical Co., Ltd., or Otsuka, in Europe and the Asia-Pacific region, respectively. Throughout 2022 and 2023, we reported positive data from the Phase 2 study and Phase 2 OLE study, including
    two-year OLE data. We are preparing to submit an NDA to the FDA. Otsuka is preparing to submit a Marketing Authorization Application, or MAA, to the EMA. In September 2023 and February 2024, the FDA and EMA, respectively, granted Orphan Drug
    designation to donidalorsen.</div>

  <div><br/>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Zilganersen is our medicine in development for Alexander disease, or AxD. In July 2024, we completed enrollment in the Phase 3 portion of
    the ongoing study for patients with AxD. In September 2020 and October 2019, the FDA and EMA, respectively, granted Orphan Drug designation to zilganersen. Additionally in August 2020, the FDA granted rare pediatric designation to zilganersen.</div>

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    </div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ulefnersen is our medicine in development for amyotrophic lateral sclerosis, or ALS, with mutations in the fused in sarcoma gene, or FUS.
    We are currently conducting a Phase 3 study of ulefnersen in juvenile and adult patients with FUS-ALS. In August 2023 and September 2023, the FDA and EMA, respectively, granted Orphan Drug designation to ulefnersen.</div>

  <div><br/>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">QALSODY is our marketed medicine to treat patients with SOD1-ALS. In April 2023, the FDA granted Biogen accelerated approval and in May
    2024, the EMA granted Biogen marketing authorization under exceptional circumstances of QALSODY for patients with SOD1-ALS. Additionally, Biogen is evaluating QALSODY as a potential treatment for presymptomatic SOD1-ALS patients in the ongoing ATLAS
    study. In September 2016 and August 2016, the FDA and EMA, respectively, granted Orphan Drug designation to QALSODY.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pelacarsen is our medicine in development to treat patients with elevated lipoprotein(a)-driven cardiovascular disease, or Lp(a)-driven
    CVD. Novartis is developing pelacarsen, including conducting the ongoing Lp(a) HORIZON Phase 3 cardiovascular outcome study in patients with elevated Lp(a)-driven CVD, which achieved full enrollment in July 2022 with more than 8,000 patients. In April
    2020, the FDA granted Fast Track designation to pelacarsen.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Bepirovirsen is our medicine in development for chronic hepatitis B virus, or HBV. GSK is developing bepirovirsen, including conducting
    the ongoing B-Well Phase 3 program in patients with HBV, which achieved full enrollment in June 2024. GSK reported positive results from Phase 2 studies in 2023, including durable response data from the Phase 2 B-Sure long-term follow-up study of
    bepirovirsen in complete responder patients from the Phase 2b B-Clear study of patients with HBV. In February 2024, the FDA granted Fast Track designation to bepirovirsen for the treatment of patients with HBV.</div>

  <div><br/>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">IONIS-FB-L<sub>Rx</sub> is our medicine in development for immunoglobulin A, or IgA, nephropathy, or IgAN. In the second quarter of 2023,
    Roche advanced IONIS-FB-L<sub>Rx</sub> into Phase 3 development in patients with IgAN. In October 2023, we reported positive interim data from the ongoing Phase 2 study of IONIS-FB-L<sub>Rx</sub> in patients with IgAN.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="CriticalAccountingEstimatesQ2"><!--Anchor--></a>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/>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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; and</div>
        </td>

  </tr>


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 appropriate estimate of anticipated future royalty payments under our royalty purchase agreement</div>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There have been no 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 December 31, 2023.</div>

  <div><br/>
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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="ResultsofOperationsQ2Q3"><!--Anchor--></a>Results of Operations</div>

  <div><br/>
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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 financial results (in millions):</div>

  <div><br/>
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        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

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    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

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    <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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">225.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">188.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">344.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">318.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</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;">Total operating expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">291.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">278.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">560.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">523.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(66.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(90.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(215.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(204.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(66.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(85.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(209.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(209.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">23</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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-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 revenue for the three and </span>six months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> were $</span>225.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>344.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, respectively, compared to $</span>188.4<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>318.9<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the same periods in </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and were comprised of the following (in millions):</span></div>

  <div><br/>
  </div>

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


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">95.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">111.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">WAINUA royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <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;">Other commercial revenue:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%;">
          <div style="text-align: left; text-indent: -18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA revenue, net</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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: -18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 other commercial revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">131.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">145.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development revenue:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Amortization from upfront payments</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Milestone payments</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">51.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">73.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">License fees</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other services</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaborative agreement revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">141.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">91.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">190.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">129.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;">
          <div style="text-align: left; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA joint development revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research and development revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">153.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">110.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">213.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">173.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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: 81pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">225.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">188.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">344.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">318.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#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;">Commercial revenue in the three and six months ended June 30, 2024 included a new source of royalty revenue with the launch of WAINUA in
    the U.S. in late January 2024. Our commercial revenue in the three and six months ended June 30, 2024 also included royalties from the net sales of QALSODY, which Biogen launched in the U.S. in the second quarter of 2023 and in the EU in the second
    quarter of 2024.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue in the three and six months ended June 30, 2024 increased compared to the same periods in 2023 primarily due to the
    amortization of upfront payments from the new collaborations with Roche and Novartis that we entered into during the second half of 2023. In addition, license fees increased year over year as a result of new collaborations we entered into during the
    second quarter of 2024, including the expanded donidalorsen licensing agreement with Otsuka, which now includes the Asia-Pacific region in addition to Europe. These increases were partially offset by the decrease in WAINUA joint development revenue,
    which decreased as development activities relating to ATTRv-PN wound down with the launch of WAINUA for this indication.</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;">WAINUA (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 three and six months ended&#160;June 30, 2024 and 2023
    reflected the cost-sharing provisions related to our collaboration with AstraZeneca to develop and commercialize WAINUA for the treatment of ATTR. Under the terms of the collaboration agreement, AstraZeneca is currently paying 55 percent of the costs
    associated with the ongoing global Phase 3 development program. Because we are leading and conducting the Phase 3 development program, we are recognizing as 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.</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 WAINUA 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. We expect our medical affairs and commercialization expenses to increase with the launch of WAINUA for ATTRv-PN in the U.S. and as WAINUA advances toward the market for ATTR-CM under our
    collaboration with AstraZeneca.</div>

  <div><br/>
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">24</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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;">The following table sets forth information on revenue and expenses under this collaboration (in millions):</div>

  <div><br/>
  </div>

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


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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;">WAINUA joint development revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Research and development expenses related to Phase 3 development of WAINUA</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">85.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 for WAINUA</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Commercialization expenses for WAINUA</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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-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;">The following table sets forth information on operating expenses (in millions):</div>

  <div><br/>
  </div>

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


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">260.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">252.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">498.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">469.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">291.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">278.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">560.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">523.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Operating expenses, excluding non-cash compensation expense related to equity awards, for the three and six months ended June 30, 2024
    increased compared to the same periods in 2023. Our SG&amp;A expenses increased year over year primarily due to the launch of WAINUA in the U.S. and launch preparation activities for olezarsen and donidalorsen, including establishing the field team for
    olezarsen. Our R&amp;D expenses <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">decreased in the three months ended June 30, 2024 compared to the same period in 2023, and were relatively consistent in the six months ended
      June 30, 2024 compared to the same period in 2023</span> as several late-stage studies have ended. We expect our operating expenses, excluding non-cash compensation expense related to equity awards, to continue to increase during the remainder of
    2024 as we advance our commercialization activities.</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<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; 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 TEGSEDI and WAYLIVRA 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;">The following table sets forth information on cost of sales (in millions):</div>

  <div><br/>
  </div>

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


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br/>
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">25</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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; 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 drug discovery, drug development, medical affairs, 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 cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">199.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">210.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">391.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">388.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">222.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">229.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">436.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">427.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;"><span style="text-decoration: underline;">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 technologies 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 drug discovery research, and that of our partners. Drug discovery is also the function that is responsible for advancing our core technology. This function is also responsible for making
    investments in complementary technologies to expand the reach of our technologies.</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 drug discovery expenses (in millions):</div>

  <div><br/>
  </div>

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


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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;">Drug discovery expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 drug discovery expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Drug discovery expenses, excluding non-cash compensation expense related to equity awards, were relatively consistent in the three
      months ended June 30, 2024 compared to the same period in 2023, and increased in the six months ended June 30, 2024 compared to the same period in 2023 as we continued to advance our technology.</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;">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>

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


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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;">WAINUA</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">TEGSEDI and WAYLIVRA</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Olezarsen</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Donidalorsen</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Zilganersen</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Ulefnersen</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Other development projects</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Development overhead expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 drug development expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">134.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">260.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">252.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 drug development expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">144.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">145.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">280.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">269.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 drug development expenses, excluding non-cash compensation expense related to equity awards, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">were relatively consistent in the three months ended June 30, 2024 compared to the same period in 2023, and increased in the six months ended June 30, 2024 compared to the same period in 2023</span> due
    to the timing of our late-stage program activities. We expect our development expenses will stabilize as several late-stage studies end and we reallocate resources toward earlier stage programs.</div>

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

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">26</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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. Because we always have numerous
    medicines in preclinical and varying stages of 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 funding and coordinating investigator-sponsored trials, communicating scientific and
    clinical information to healthcare providers, medical professionals and patients, and managing publications.</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 medical affairs expenses (in millions):</div>

  <div><br/>
  </div>

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


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Medical affairs expenses, excluding non-cash compensation expense related to equity awards, increased in the three and six months
      ended June 30, 2024 compared to the same periods in 2023 as we continued advancing 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, validation batches to support regulatory approvals, laboratory supplies and outside services. Our manufacturing and development chemistry function is responsible for providing drug supplies to 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;">The following table sets forth information on manufacturing and development chemistry expenses (in millions):</div>

  <div><br/>
  </div>

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


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">36.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Manufacturing and development chemistry expenses, excluding non-cash compensation expense related to equity awards, decreased in the three
    and six months ended June 30, 2024 compared to the same periods in 2023. In the three and six months ended June 30, 2023, our contract manufacturing organizations, or CMOs, manufactured higher quantities of drug product related to several late-stage
    programs.</div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">27</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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, information technology costs, procurement costs and waste disposal costs. We call these costs R&amp;D support expenses<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;">The following table sets forth information on R&amp;D support expenses (in millions):</div>

  <div><br/>
  </div>

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


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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;">Computer software and licenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 R&amp;D support expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 R&amp;D support expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">R&amp;D support expenses, excluding non-cash compensation expense related to equity awards, were relatively consistent in the three and
    six months ended June 30, 2024 compared to the same periods in 2023.</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;">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 SG&amp;A 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 and QALSODY.</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>

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


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">101.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">117.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">91.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 in the three and six months ended
      June 30, 2024 compared to the same periods in 2023 due to increased expenses related to our launch of WAINUA and launch preparation activities for olezarsen and donidalorsen.</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 cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">51.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 due to an increase in interest rates associated with our investments during the three and six months ended
    June 30, 2024 compared to the same periods in 2023.</div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">28</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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;">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 cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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;">Convertible notes:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#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 mortgage for manufacturing facility</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#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;">In June 2023, we completed a $575.0 million offering of our 1.75% Notes and repurchased $504.4 million in principal of our 0.125% Notes.
    As a result, beginning in the second quarter of 2023, our interest expense related to our convertible notes increased because we began incurring interest expense for our 1.75% Notes.</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 Related to Sale of Future Royalties</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 recorded $</span>18.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>36.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of interest expense related to the sale of future royalties in the three and </span>six months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively, compared to $</span>17.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>33.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in the same periods in </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively. These amounts are related to the Royalty Pharma transaction, in which we sold a minority interest in our future royalties to Royalty Pharma for a $500 million upfront payment and
      $625 million of potential future payments. Refer to </span>Part I, Item 1, Note 11, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Liability Related to Sale of Future Royalties</span>, in the Notes
    to Condensed Consolidated Financial Statements for further details.</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;">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 cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <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;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 driven by changes in the fair value of our investments in
    privately held and publicly traded 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 2023, we completed a $575.0 million offering of our 1.75% Notes and used $420.4 million of the net proceeds to
    repurchase $434.1 million in principal of our 0.125% Notes. As a result, we recorded an $11.3 million gain on early retirement of debt in the second quarter of 2023, which reflects the difference between the amount we paid to repurchase a portion of
    our 0.125% Notes and the net carrying balance of the liability at the time that we repurchased the debt. Refer to Part I, Item 1, Note 12, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Convertible
      Debt</span>, in the Notes to Condensed Consolidated Financial Statements for further details regarding our convertible debt.</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;">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;">We recorded income tax expense of $0.1
    million and $0.1 million for the three and six months ended&#160;June 30, 2024, respectively, compared to $7.8 million and $19.2 million for the same periods in 2023, respectively. The decrease in income tax expense relates primarily to the impact of the royalty purchase agreement with Royalty Pharma on income tax
    expense for the three and six months ended&#160;June 30, 2023. We reflected the Royalty Pharma transaction as a taxable sale, which required us to include the proceeds from the sale, net of currently deductible issuance costs, as taxable income in 2023.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We continue to maintain a full valuation allowance on all our net deferred tax assets.</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;">Net Loss<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and Net Loss
      per Share</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We had a net loss of $66.3
    million and $209.1 million for the three and six months ended&#160;June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively. </span>We
    had a net loss of $85.3 million and $209.6
    million for the same periods in 2023. The <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">period-over-period
      fluctuations in our net loss were driven by </span>factors discussed in the sections above. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Basic and diluted net loss per share for the three and </span>six months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> were $</span>0.45<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and $</span>1.43<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively, compared to $</span>0.60<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and $</span>1.47<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
      for the same periods in </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt; font-size: 8pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman',Times,serif;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">29</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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-style: italic;"><a style="font-family: 'Times New Roman',Times,serif;" href="#Index">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="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 financed our operations from revenue from SPINRAZA and QALSODY royalties and TEGSEDI and WAYLIVRA commercial revenue. In addition, we began receiving commercial revenue from WAINUA royalties in 2024. From
      our inception through </span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have earned
      approximately</span> $7.6&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">billion in revenue. </span>We have
    also financed our operations through the sale of our equity securities, the issuance of long-term debt and the sale of future royalties<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. From the time we were founded through</span>&#160;June 30, 2024, we have raised net proceeds of approximately $2.1 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>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have borrowed approximately</span> $2.7 billion under long-term debt arrangements and received proceeds of $0.5 billion from the sale of future royalties to finance a portion of our
    operations.</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;">From </span>December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span>June 30, 2024&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">our working capital decreased as our cash, cash equivalents and short-term investments decreased.
      During the same period, our long-term obligations did not change significantly.</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 summarizes our contractual obligations, excluding our liability related to the sale of future royalties, as of<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>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 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;">Contractual Obligations</div>

  <div><br/>
  </div>

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


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="10">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 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 valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="2">
          <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 valign="bottom" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <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;">1.75% Notes (principal and interest payable)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">615.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">605.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <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% Notes (principal payable)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <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;">0.125% Notes (principal and interest payable)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">269.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">249.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <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 valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,572.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,496.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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 contractual obligations consist primarily of our convertible debt. In addition, we also have a facility mortgage, facility leases,
    equipment financing arrangements and other obligations. We believe our cash, cash equivalents and short-term investments, as well as plans for cash in the future, will be sufficient to fund our planned operations and these obligations. 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: 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;">Refer to Part I, Item 1, Note 12, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Convertible
      Debt</span>, in the Notes to Condensed Consolidated Financial Statements for the significant terms of each convertible debt instrument.</div>

  <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;">Operating Facilities</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Part IV, Item 15, Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term
      Obligations and Commitments</span>, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2023 for further details on our operating 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;">Operating Leases</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Part IV, Item 15, Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term
      Obligations and Commitments</span>, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2023 for further details on our operating leases.</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;">Liability Related to Sale of Future Royalties</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Part I, Item 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 11, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Liability Related to Sale of Future Royalties, </span>in the Notes to Condensed Consolidated Financial Statements for further details on our royalty purchase
    agreement with Royalty Pharma<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">30</span></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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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; font-style: italic; font-weight: bold;">Other Obligations</div>

  <div><br/>
  </div>

  <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 June 30, 2024&#160;<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>

  <div><br/>
  </div>

  <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, securing lines of credit or executing royalty monetization agreements. 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>

  <div><br/>
  </div>

  <div><br/>
  </div>

  <div><a id="ITEM3MarketRisk"><!--Anchor--></a></div>
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  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 3.</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-weight: bold;">QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK</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;">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>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

  <div><a id="Item4Controls"><!--Anchor--></a></div>
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  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 4.</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-weight: bold;">CONTROLS AND PROCEDURES</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;">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>

  <div><br/>
  </div>

  <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 June 30, 2024. <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>&#160;June 30, 2024.</div>

  <div><br/>
  </div>

  <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>

  <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;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">31</span></div>

    </div>

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      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </div>

  <div style="text-align: left;"><a id="PARTII"><!--Anchor--></a><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART II &#8212; OTHER INFORMATION</div>

  <div><br/>
  </div>

  <div><a id="ITEM1"><!--Anchor--></a></div>
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  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 1.</span></td>

    <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>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For details of legal proceedings, refer to Part I, Item 1, Note 13, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Legal Proceedings</span>, in the Notes to Condensed Consolidated Financial Statements<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

  <div><br/>
  </div>

  <div><a id="ITEM1A"><!--Anchor--></a></div>
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  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 1A.</span></td>

    <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>

  </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;">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, 2023.</div>

  <div><br/>
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Summary of Risk Factors</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; 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>

  <div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 ability to generate substantial revenue from the sale of our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">&#932;</span>he availability of adequate coverage and payment rates for our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 and our partners&#8217; ability to compete effectively;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 ability to successfully manufacture our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 ability to successfully develop and obtain marketing approvals for our medicines;</div>
        </td>

  </tr>


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    <td style="width: 18pt; vertical-align: top; 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 ability to secure and maintain effective corporate partnerships;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 ability to sustain cash flows and achieve consistent profitability;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 ability to protect our intellectual property;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 ability to maintain the effectiveness of our personnel;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 impacts of health epidemics, climate change, war and other global events;</div>
        </td>

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</table>
  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;&#160; &#160;&#160; Our dependence upon our own and third-party information technology systems;</div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;&#160; &#160;&#160; Our compliance with laws; and</div>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 other factors set forth below.</div>
        </td>

  </tr>


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  <div><br/>
  </div>

  <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>

  <div>
    <div><br/>
    </div>

  </div>

  <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 continue to invest significant resources to
    develop our 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>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We currently rely on third parties for the commercialization of our marketed medicines, have limited experience as a company in
    commercializing medicines and will have to continue 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 continue 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.
    If we continue to 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>

  <div><br/>
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    </div>

  </div>

  <div><br/>
  </div>

  <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 our commercial medicines and our medicines in development, we are not likely to
    generate substantial revenues or become consistently profitable.</div>

  <div><br/>
  </div>

  <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 United States, or U.S., Food and Drug Administration, or 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>

  <div><br/>
  </div>

  <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, 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 our commercial medicines 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 in the past disclosed that SPINRAZA revenue decreased in part due to lower pricing in the U.S. and certain rest-of-world markets.</div>

  <div><br/>
  </div>

  <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 our commercial medicines and our medicines in development, depends upon a
    number of factors, including the:</div>

  <div><br/>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">receipt and scope of marketing authorizations;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">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: 18pt; vertical-align: top; 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;">cost and effectiveness of our medicines compared to other available therapies;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">patient convenience of the dosing regimen for our medicines; and</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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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</table>
  <div><br/>
  </div>

  <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 of the medicines that we or our partners may develop.</div>

  <div><br/>
  </div>

  <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 and is available in the U.S. only through a risk evaluation and
    mitigation strategy, or REMS program. In addition, the product label for TEGSEDI in the U.S. has a boxed warning for thrombocytopenia and glomerulonephritis. Our main external 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.</div>

  <div><br/>
  </div>

  <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 our commercial
    medicines 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, our commercial medicines and our medicines in development will face competition from other therapies and medicines for limited financial
    resources. Furthermore, 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. In addition, third-party payers may never consider our future products as cost-effective and 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>

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    </div>

  </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, or ACA, 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 ACA, as well as efforts to repeal or replace certain aspects of the ACA. It is unclear how future litigation and healthcare reform measures will impact the ACA 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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, increase competition (including by enhancing support for generic and biosimilar drugs), lower out-of-pocket drug costs for
      patients, curtail spread pricing practices by pharmacy benefit managers, and foster scientific innovation to promote better health care and improved health. In addition, the Inflation Reduction Act of 2022, or the IRA, includes key actions aimed at
      reducing the costs of prescription drugs and allows HHS to negotiate the price of certain single-source drugs covered under Medicare and establish a price cap on such drugs. Specifically, in an effort to curb Medicare patients&#8217; out-of-pocket costs
      for prescription drugs, the Part D redesign legislation under the IRA requires, among other things, (1) </span>a cap on out-of-pocket drug spending under Part D, (2) drug manufacturers to pay a rebate to the federal government if prices for drugs
    covered under Part D and Part B increase faster than the rate of inflation, and (3) drug<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> manufacturers to contribute to the catastrophic coverage phase for Part D drugs as
      discounts through a manufacturer discount program. The IRA permits HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years. These provisions take effect progressively starting in fiscal year 2023.
      On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges. In response to the Biden administration&#8217;s
      October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the CMS Innovation Center which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve
      quality of care. It is unclear whether the models will be utilized in any health reform measures in the future. Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs using march-in
      rights under the Bayh-Dole Act. On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the
      price of a product as one factor an agency can use when deciding to exercise march-in rights. While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework. It is unclear whether or how these
      selected models or similar policy initiatives will impact prescription drug pricing in the future.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Any reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payments from private
    payers. Our future product sales may be subject to additional discounts from list price in the form of rebates and discounts provided to covered entities under the Public Health Service Act 340B drug pricing program. Changes to the 340B program or to
    Medicare or Medicaid programs at the federal or state level, including outcomes of ongoing litigation in our industry, may impact our product prices and rebate liability.</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. For example, on January 5, 2024, the FDA approved Florida&#8217;s Section 804 Importation Program, or SIP, proposal to import certain drugs from Canada for specific state healthcare programs. It is unclear how this
    program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the United States or Canada. Other states have also submitted SIP proposals that are pending review by the FDA. Any such approved
    importation plans, when implemented, may result in lower drug prices for products covered by those programs. Third-party coverage and reimbursement for medicines may not be available or adequate in either the U.S. or international markets, which would
    negatively affect the potential commercial success of our products, our revenue and our profits.</div>

  <div><br/>
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    </div>

  </div>

  <div><br/>
  </div>

  <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 our commercial medicines and our medicines in development,
    will not generate significant revenues.</div>

  <div><br/>
  </div>

  <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. In addition, other companies are engaged in developing RNA-targeted technology. Our competitors may succeed in developing medicines that are:</div>

  <div><br/>
  </div>

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    <td style="width: 18pt; vertical-align: top; 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;">priced lower than our medicines;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; 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;">reimbursed more favorably by government and other third-party payers than our medicines;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">safer than our medicines;</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">more effective than our medicines; or</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">more convenient to use than our medicines.</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;">These competitive developments could make our medicines, including our commercial medicines and our medicines in development, obsolete or
    non-competitive.</div>

  <div><br/>
  </div>

  <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 some of 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 our commercial medicines 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;">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 or more successfully commercialize their products.</div>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">Onasemnogene abeparvovec and risdiplam compete with SPINRAZA;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">Taldefgrobep alfa, Evrysdi + GYM329 and NMD670 could compete with SPINRAZA;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">Patisiran, tafamidis, tafamidis meglumine and vutrisiran compete with TEGSEDI and WAINUA;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">Acoramidis, NTLA-2001 and NNC6019-0001 could compete with TEGSEDI and WAINUA;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 and pegozafermin could compete with WAYLIVRA and olezarsen;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">Lanadelumab-flyo, C1 esterase inhibitor, berotralstat, C1 esterase inhibitor subcutaneous,
              garadacimab, </span>deucrictibant,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160; NTLA-2002 and STAR-0215 could compete with donidalorsen;</span></div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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; 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;">Olpasiran, </span>zerlasiran, lepodisiran and muvalaplin <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">could compete with pelacarsen;</span></div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">NI-005/AP-101 could compete with QALSODY;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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; 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;">VIR-2218 + PEG-IFN-&#945;, VIR-3434 &#177; VIR-2218 &#177; PEG-IFN-&#945;, VIR-2218 + BRII-179, NI-204VIR-2218 + GS-9688 + nivolumab, AB-729, imdusiran + Peg-IFNa-2&#945; + NA, xalnesiran +
            RG6084 + NA, xalnesiran + NA, xalnesiran + pegIFN + NA, xalnesiran + RO7049389 + NA, xalnesiran + ruzotolimod + NA, RO7049389 + ruzotolimod + NA could complete with bepirovirsen; and</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">Budesonide, sparsentan, atrasentan, iptacopan, zigakibart, sibeprenlimab, atacicept, ravulizumab, vemircopan, felzartamab, povetacicept, avacincaptad pegol,
            pegcetacoplan, tinlarebant, danicopan, GT005, AVD-104 and ANX007 could compete with IONIS-FB-L<sub>Rx</sub>.</div>
        </td>

  </tr>


</table>
  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 in the past disclosed that SPINRAZA revenue decreased 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.</div>

  <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;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">35</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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</span>.</div>

  <div><br/>
  </div>

  <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 our commercial medicines 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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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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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</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <div><br/>
  </div>

  <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 indication(s) in accordance with the approved label. The FDA and other
    regulatory authorities 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>

  <div><br/>
  </div>

  <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 authorities 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>

  <div><br/>
  </div>

  <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 CMOs 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.</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 collaborations with Biogen for the development and commercialization of SPINRAZA and QALSODY.</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 separate collaborative arrangements with Biogen to develop and commercialize SPINRAZA and QALSODY. We entered into
    these collaborations primarily to:</div>

  <div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 and QALSODY;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 QALSODY; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 and QALSODY.</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;">We are relying on Biogen to obtain additional regulatory approvals for SPINRAZA and QALSODY, generate additional clinical data for
    SPINRAZA and QALSODY, manufacture SPINRAZA and QALSODY, and successfully commercialize SPINRAZA and QALSODY. In general, we cannot control the amount and timing of resources that Biogen devotes to our collaborations. If Biogen fails to further develop
    SPINRAZA or QALSODY, obtain additional regulatory approvals for SPINRAZA or QALSODY, manufacture SPINRAZA or QALSODY, or successfully commercialize SPINRAZA or QALSODY, or if Biogen&#8217;s efforts in any of these respects are ineffective, revenues for
    SPINRAZA or QALSODY would 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;">In addition, our collaborations with Biogen may not continue for various reasons. Biogen can terminate our collaborations at any time. If
    Biogen stops developing or commercializing SPINRAZA or QALSODY, we would have to seek or spend additional funding, and SPINRAZA&#8217;s or QALSODY&#8217;s commercialization may be harmed.</div>

  <div><br/>
  </div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">36</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </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 AstraZeneca for the joint development and commercialization of WAINUA.</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 WAINUA. Under the terms of the
    collaboration agreement, we and AstraZeneca will co-develop and co-commercialize WAINUA in the U.S. and AstraZeneca will have the sole right to commercialize WAINUA in all other countries. 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 WAINUA is not successful
    for any reason, WAINUA may not meet our commercial objectives and our revenues for WAINUA 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 WAINUA 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 WAINUA.</div>

  <div><br/>
  </div>

  <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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">To successfully commercialize any of our medicines, we 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. While</span> we believe <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">our current capabilities and those we obtain through third-party manufacturers support our
      manufacturing needs now, it will be important to expand our manufacturing infrastructure in the future, which will likely require substantial expenditures. 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.</span></div>

  <div><br/>
  </div>

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

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 our commercial medicines and our medicines in development, or could result in enforcement action after authorization that might limit the commercial success of our
    medicines, including our commercial medicines 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We rely on third-party manufacturers to supply the drug
      substance and drug product for TEGSEDI and WAINUA and drug product for WAYLIVRA. Any delays or disruption to our own or third-party commercial manufacturing capabilities could limit the commercial success of our medicines</span>.</div>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

  <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 our commercial medicines, we or
    our partners cannot sell them in the applicable markets.</div>

  <div><br/>
  </div>

  <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 our commercial medicines 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>

  <div><br/>
  </div>

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    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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 and our partners may not obtain necessary regulatory approvals on a timely basis, if at all, for our medicines. It is possible that
    regulatory authorities will not approve our medicines for marketing or our commercial medicines in additional markets or for additional indications. If the FDA or another regulatory authority believes that we or our partners have not sufficiently
    demonstrated the safety or efficacy of any of our medicines, including our commercial medicines or our medicines in development, the authority will not approve the specific medicine or will require additional studies, which could be time consuming and
    expensive and 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 Notice of Non-Compliance Withdrawal Letter, or Non-W, from Health Canada for WAYLIVRA in
    November 2018.</div>

  <div><br/>
  </div>

  <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>

  <div><br/>
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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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</table>
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    <td style="width: 18pt; vertical-align: top; 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 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: 18pt; vertical-align: top; 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 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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</table>
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    <td style="width: 18pt; vertical-align: top; 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 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: 18pt; vertical-align: top; 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 disagree with the interpretation of data from preclinical or clinical studies;</div>
        </td>

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</table>
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    <td style="width: 18pt; vertical-align: top; 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; and</div>
        </td>

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</table>
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    <td style="width: 18pt; vertical-align: top; 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 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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</table>
  <div><br/>
  </div>

  <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 in development, or failure to receive additional marketing authorizations for
    our commercial medicines, 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>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug discovery and drug development have 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(s), we may need to abandon one or more of our drug development programs.</div>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

  <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 do not show sufficient safety and 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>

  <div><br/>
  </div>

  <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 QALSODY did not meet the primary clinical endpoint in the Phase 3 VALOR study; however, trends favoring QALSODY 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.</div>

  <div><br/>
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    </div>

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    </div>

  </div>

  <div><br/>
  </div>

  <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>

  <div><br/>
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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: 18pt; vertical-align: top; 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;">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: 18pt; vertical-align: top; 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, 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: 18pt; vertical-align: top; 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 or our partners may decide, or regulators may require us, to conduct additional preclinical testing or clinical studies;</div>
        </td>

  </tr>


</table>
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    <td style="width: 18pt; vertical-align: top; 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;">enrollment in our clinical studies may be slower than we anticipate;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; 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 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 or 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: 18pt; vertical-align: top; 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 institutional review board for a prospective site might withhold or delay its approval for the study;</div>
        </td>

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</table>
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    <td style="width: 18pt; vertical-align: top; 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;">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>
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    <td style="width: 18pt; vertical-align: top; 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 clinical study site may deviate from the protocol for the study;</div>
        </td>

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</table>
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    <td style="width: 18pt; vertical-align: top; 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 cost of our clinical studies may be greater than we anticipate;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; 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 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: 18pt; vertical-align: top; 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 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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</table>
  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Further, the FDA or other regulatory authorities could request, among other things, 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. In addition, under accelerated approval the FDA is requiring completion of the
    ongoing Phase 3 trial for QALSODY to confirm the clinical benefit of QALSODY.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Moreover, our commercial medicines 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. Any failure or delay in our clinical studies could reduce the commercial potential or viability of our medicines.</div>

  <div><br/>
  </div>

  <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 clinical studies for our medicines and any failure of those parties to fulfill their obligations
    could adversely affect our development and commercialization plans.*</div>

  <div><br/>
  </div>

  <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, Medpace, Inc., Parexel International Corporation, Syneos Health, Inc. and
    Thermo Fisher Scientific Inc. for the clinical studies for our medicines, including WAINUA for the treatment of ATTR-CM, donidalorsen, olezarsen, ulefnersen and zilganersen. 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, but we are responsible for ensuring that such investigators 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 have in the past experienced labor shortages, which impacted their ability to perform services for us for certain of our clinical trials. Subsequent failures of these third parties to carry out their obligations, or a termination of our
    relationship with such third parties, could delay or prevent the development, marketing authorization and commercialization of our medicines.</div>

  <div><br/>
  </div>

  <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 Russia, Ukraine or Gaza, we do have a limited number of clinical trial sites
    in Israel that may be materially impacted by the ongoing military conflicts in Israel and elsewhere in the Middle East and could result in difficulties enrolling or completing our clinical trials in such areas on schedule.</div>

  <div><br/>
  </div>

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    </div>

  </div>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

  <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 some 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>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our corporate partners are developing and funding many of the medicines in our development pipeline. For example, we are relying on:</div>

  <div><br/>
  </div>

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    <td style="width: 18pt; vertical-align: top; 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 WAINUA;</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 for development and funding of bepirovirsen; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 IONIS-FB-L<sub>Rx</sub>.</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;">If any of these pharmaceutical companies stops developing and 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, in 2022, Pfizer and
    Bayer decided to discontinue the clinical development programs for vupanorsen and fesomersen, respectively.</div>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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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</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 and commercialize our medicines.</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;">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, Otsuka and Roche, these collaborations may not continue or result in commercialized medicines, or may not progress as quickly as we anticipated.</div>

  <div><br/>
  </div>

  <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, Otsuka or Roche, could determine that it is in its financial
    interest to:</div>

  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 to its own medicines.</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;">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 QALSODY, SPINRAZA, WAINUA, bepirovirsen, donidalorsen, IONIS-FB-L<sub>Rx</sub> and pelacarsen.</div>

  <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;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">40</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"/></div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: left; 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><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 olezarsen for the treatment of patients with FCS, to ulefnersen for the treatment of patients with FUS-ALS, and to ION582
    for the treatment of patients with Angelman syndrome. The FDA and European Medicines Agency, or EMA, have granted Orphan Drug designation to WAINUA for the treatment of patients with ATTR, to donidalorsen for the treatment of patients with HAE, to
    TEGSEDI for the treatment of patients with ATTRv-PN, to WAYLIVRA for the treatment of patients with FCS, to tominersen for the treatment of patients with HD, and to ION356 for the treatment of patients with Pelizaeus-Merzbacher disease. 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 or a
    substantially similar 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>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

  <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: 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>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Many of our medicines are undergoing clinical studies or are in the early stages of research and development. Most of our 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. In
    addition, as we commercialize more medicines on our own, we will need to invest significant financial resources to continue developing the infrastructure required to successfully commercialize our medicines, including the expansion of our manufacturing
    capabilities. All of these activities will require significant cash. As of June 30, 2024, we had cash, cash equivalents and short-term
    investments equal to $2.1 billion. If we or our partners do not meet our goals to successfully commercialize our medicines, including our
    commercial medicines, 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:</div>

  <div><br/>
  </div>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">successful commercialization of our commercial medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 in development;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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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</table>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <div><br/>
  </div>

  <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 on
    acceptable terms or at all. 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, or commercial operations. 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>

  <div><br/>
  </div>

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    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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;">We have incurred losses, and our business will suffer if we fail to consistently achieve profitability in the future.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Because drug discovery and development require substantial lead-time and money prior to commercialization, our expenses have generally
    exceeded our revenue since we were founded in January 1989. As of June 30, 2024, we had an accumulated deficit of approximately $2.0 billion and stockholders&#8217; equity of approximately $0.3
    billion. Most of our income has historically 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. We will now and continuing into the foreseeable future need to invest significant financial resources to develop capabilities to commercialize medicines on our own and expect that our income in the future will be driven primarily by
    commercial sales. If we do not earn substantial revenue from commercial sales, we may incur additional operating losses in the future, which could restrict our ability to successfully develop additional medicines or sustain future profitability.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We may not be entitled to obtain additional milestone payments under our royalty monetization agreement with Royalty Pharma.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a Royalty Purchase Agreement with Royalty Pharma Investments. In addition to the $500 million we received
    at closing, this agreement makes available to us up to an additional $625 million in milestone payments. However, these additional milestone payments are subject to satisfaction of certain conditions related to the regulatory approval or commercial
    sales of pelacarsen, in certain cases by specific deadlines. Should we not satisfy such conditions by the applicable deadlines, or if we fail to meet our obligations or default under this agreement, the actual amount of additional payments to us could
    be substantially less than the maximum amounts available thereunder.</div>

  <div><br/>
  </div>

  <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, any of 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>

  <div><br/>
  </div>

  <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 our commercial medicines, 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>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we or any licensor partner loses or cannot obtain patent protection for our commercial medicines or any of our medicines in
    development, it could have a material adverse impact on our business.</div>

  <div><br/>
  </div>

  <div style="text-align: left; 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>

  <div><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 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>

  <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;">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 product liability</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 our commercial medicines 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;">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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are dependent on the principal members of our management
      and scientific staff, and as we move towards commercializing medicines on our own, we will become increasingly dependent on the principal members of our commercial team. We do not have employment agreements with any of our employees that would
      prevent them from leaving us. The loss of our management, key scientific or commercial employees might slow the achievement of important research and development or commercial goals. It is also critical to our success that we recruit and retain
      qualified scientific personnel to perform research and development work and that we recruit and retain qualified marketing, sales, market access, distribution, and related personnel to commercialize our medicines. We may not be able to attract and
      retain skilled and experienced personnel on acceptable terms because of intense competition for experienced personnel among many pharmaceutical and health care companies, universities and non-profit research institutions. In addition, failure to
      succeed in clinical studies or in commercializing our medicines may make it more challenging to recruit and retain qualified personnel</span>.</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 health epidemics, climate change and other events</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 health epidemics, climate change, extreme weather events, earthquakes, war, civil or political
    unrest, terrorism or other catastrophic events.</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 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 disruption in the operations of third-party manufacturers and contract research organizations upon whom we rely. For example, enrollment in some of our clinical trials
    was 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;">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. We manufacture the finished drug product for TEGSEDI, WAINUA and WAYLIVRA at third-party contract manufacturers. Biogen manufactures the finished drug product for SPINRAZA and QALSODY. 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.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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, 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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to cybersecurity, social media and artificial intelligence</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, particularly as companies (including us) moved to more remote work structures during and following 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 and military conflicts in Israel and the
    surrounding areas, as well as related political or economic responses and counter-responses by various global actors, or collectively, conflicts in Eastern Europe and the Middle East.</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, delay progress on the development of our medicines, 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.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">The increasing use of social media platforms and artificial intelligence based software presents new risks and challenges.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Social media is increasingly being used to communicate about our medicines and the diseases our therapies are designed to treat. Social
    media practices in the biopharmaceutical industry continue to evolve and regulations relating to such use are not always clear and create uncertainty and risk of noncompliance with regulations applicable to our business. There is also a risk of
    inappropriate disclosure of sensitive information or negative or inaccurate posts or comments about us on social media. We may also encounter criticism on social media regarding our company, management, or medicines. Our reputation could be damaged by
    negative publicity or if adverse information concerning us is posted on social media platforms or similar mediums, which we may not be able to reverse. If any of these events were to occur or we otherwise fail to comply with applicable regulations, we
    could incur liability, face restrictive regulatory actions or incur other harm to 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;">Additionally, artificial intelligence, or AI, based software is increasingly being used in the biopharmaceutical industry. Use of AI based
    software may lead to the release of confidential proprietary information, which may impact our ability to realize the benefit of our intellectual property.</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 securities and the global credit markets</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. If we do not achieve milestones in accordance with our or our investors&#8217; or securities analysts&#8217; expectations, including milestones
    related to our commercial medicines and medicines in development, the price of our securities could decrease.</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 June 30, 2024, the closing market price of our common stock ranged from $53.55 to $36.45 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,
    recent events such as the COVID-19 pandemic, the ongoing conflicts in Eastern Europe and the Middle East, and the failure of Silicon Valley Bank have caused disruptions of global financial markets and resulted in increased volatility in the trading
    price of our common stock. 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, bylaws, 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, chairperson 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 2023, we completed a $575 million offering of 1.75% Notes and used $488.2 million of the net proceeds from the issuance of the 1.75%
    Notes to repurchase $504.4 million of our 0.125% Notes. In 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 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 28.2 million shares of our common stock upon conversion of our 1.75% Notes, 0% Notes
      and 0.125% Notes. In connection with the issuance of the 0% Notes and 0.125% Notes, we entered into certain call spread transactions covering 10.9 million shares and 6.6 million shares, respectively, </span>that we expect will <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">offset the dilution to holders of common stock upon any conversion </span>of those notes.&#160; In addition, o<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">f the shares reserved, 6.1 million shares are reserved for issuance upon conversion of 0.125% Notes that we have repurchased and are currently held by us in treasury (and thus would not be dilutive). As a result, to the extent we elect to
      convert the 0.125% Notes held by us in treasury, we expect we would receive up to 6.1 million shares upon settlement of related convertible note hedges (without any additional dilution caused by the conversion of the 0.125% Notes held in treasury).&#160;
      However, the anti-dilutive effect of the convertible note hedges is offset by certain warrant transactions we entered into in connection with the issuance of the 0% Notes and the 0.125% Notes. The addition of any of these shares into the public
      market may have an adverse effect on the price of our securities.</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 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;">Negative conditions in the global credit markets and financial services and other industries may adversely affect our business, financial
    condition or stock price.</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 and financial markets have experienced extreme volatility and disruptions recently, including as a result of the
    COVID-19 pandemic, ongoing conflicts in Eastern Europe and the Middle East, and the failure of Silicon Valley Bank. These disruptions can result in severely diminished liquidity and credit availability, declines in consumer confidence, declines in
    economic growth, increases in unemployment rates and uncertainty about economic stability. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. If the current equity
    and credit markets deteriorate, it may make any necessary debt or equity financing more difficult, more costly and more dilutive. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect
    on our operations, growth plans, financial performance or stock price. In addition, 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.</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;">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</span>:</div>

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    <td style="width: 18pt; vertical-align: top; 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 differing or unexpected regulatory requirements for our medicines and foreign employees;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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 and export restrictions, price and exchange controls and other regulatory requirements;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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, acts of terrorism, political instability or public health issues or health epidemics, in particular
            foreign countries or globally;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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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</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>
  <div><br/>
  </div>

  <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 contract research organizations,
    contract manufacturing organizations, distributors, wholesalers, agents, contractors and other partners) will comply with anti-bribery laws. Importantly, 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>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to compliance with laws</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 extensive legal and regulatory requirements affecting the health care industry.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operations are subject to extensive legal and regulatory requirements affecting the health care industry, 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. 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.</div>

  <div><br/>
  </div>

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    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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;">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>

  <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 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>

  <div><br/>
  </div>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">interruption of our research, development and manufacturing efforts;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">injury to our employees and others;</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">environmental damage resulting in costly clean up; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="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: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; 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;">liabilities under federal, state and local laws and regulations governing health and human safety, as well as the use, storage, handling and disposal of these materials
            and resultant waste products.</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;">In such an event, we may be held liable for any resulting damages, and any liability could exceed our resources. Although we carry
    insurance for pollution liability in amounts and types that we consider commercially reasonable, 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>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

  <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 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>

  <div><br/>
  </div>

  <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. In July 2010, the Dodd-Frank Wall Street Reform and Protection Act, or the Dodd-Frank Act, was enacted, and in August 2022, the SEC adopted additional rules and regulations under the Dodd-Frank Act related to &#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 has and may in the future lead
    to additional compliance costs and impact the manner in which we operate our business.</div>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

  <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 carry forward 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>

  <div><br/>
  </div>

  <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 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>

  <div><br/>
  </div>

  <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 our merger with Akcea Therapeutics, Inc. in
    2020, or 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
    NOLs is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed.</div>

  <div><br/>
  </div>

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    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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;">Our future taxable income could be impacted by changes in tax laws, regulations and treaties.</div>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

  <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>

  <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 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. In 2021, the Organization for Economic Cooperation and Development, or OECD, announced an Inclusive Framework on Base Erosion and Profit Shifting
      including Pillar Two Model Rules defining a global minimum tax rate of 15% on a country-by-country basis for multinational corporations with annual consolidated revenue above &#8364;750 million. The ultimate impact from changes in legislation of countries
      in which we operate remains uncertain and such changes could have a material impact on our future effective tax rate. In addition, 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</span>.</div>

  <div><br/>
  </div>

  <div><a id="ITEM2"><!--Anchor--></a></div>
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  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 2.</span></td>

    <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>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>

  <div><br/>
  </div>

  <div><a id="ITEM3"><!--Anchor--></a></div>
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    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 3.</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-weight: bold;">DEFAULT UPON SENIOR SECURITIES</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;">Not applicable.</div>

  <div><br/>
  </div>

  <div><a id="ITEM4"><!--Anchor--></a></div>
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  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 4.</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-weight: bold;">MINE SAFETY DISCLOSURES</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;">Not applicable.</div>

  <div><br/>
  </div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">49</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </div>

  <div><br/>
  </div>

  <div><a id="ITEM5"><!--Anchor--></a></div>
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  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 5.</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-weight: bold;">OTHER INFORMATION</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div style="text-align: left; text-indent: -72pt; margin-left: 72pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Trading Plans</div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="ecd:MtrlTermsOfTrdArrTextBlock" id="Text_40cf79e999b74fe080634a082436c245" contextRef="c20240401to20240630" escape="true" continuedAt="Text_d96577c065e94f6cbad1c6e9e8b50a501">
<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 quarter ended June 30, 2024, our Section 16 officers and directors adopted or terminated contracts, instructions or written plans for the purchase or sale of our securities as noted in the table below.</div>
</ix:nonNumeric>

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  </div>
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    <td style="width: 18pt; vertical-align: top; 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;">Contract, instruction or written plan intended to satisfy the affirmative defense conditions of Rule 10b5-1(c) under the Exchange Act.</div>
        </td>

  </tr>


</table>
</ix:continuation>
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    <td style="width: 18pt; vertical-align: top; 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;">&#8220;Non-Rule 10b5-1 trading arrangement&#8221; as defined in item 408(c) of Regulation S-K under the Exchange Act.</div>
        </td>

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</table>
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    <td style="width: 15.11%; vertical-align: top;" rowspan="2">

        </td>

    <td style="width: 2.22%; vertical-align: top;" rowspan="2">&#160;</td>

    <td style="width: 11.78%; vertical-align: bottom; border-bottom: #000000 2px solid;" rowspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Action</div>
        </td>

    <td style="width: 2.54%; vertical-align: bottom;" rowspan="2">&#160;</td>

    <td style="width: 10.16%; vertical-align: bottom; border-bottom: #000000 2px solid;" rowspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Date</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom;" rowspan="2">&#160;</td>

    <td style="width: 19.44%; vertical-align: bottom; border-bottom: #000000 2px solid;" colspan="3">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Trading Arrangement</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom;" rowspan="2">&#160;</td>

    <td style="width: 10%; vertical-align: bottom; border-bottom: #000000 2px solid;" rowspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Shares to Be Sold</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom;" rowspan="2">&#160;</td>

    <td style="width: 22.1%; vertical-align: bottom; border-bottom: #000000 2px solid;" rowspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration Date</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.98%; vertical-align: bottom; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Rule 10b5-1*</div>
        </td>

    <td style="width: 2.22%; vertical-align: top; border-top: #000000 2px solid;">&#160;</td>

    <td style="width: 9.24%; vertical-align: bottom; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="ecd:NonRule10b51ArrAdoptedFlag" id="Fact_d1fd16db2ebd4b5e9132e1c6daa084c5" contextRef="c20240401to20240630_IndividualAxis_RichardSGearyMember" format="ixt:fixed-false"><ix:nonNumeric name="ecd:NonRule10b51ArrTrmntdFlag" id="Fact_cfd744dc6e6048fcba95ce928a641f72" contextRef="c20240401to20240630_IndividualAxis_BrettMoniaMember" format="ixt:fixed-false">Non-Rule 10b5-1</ix:nonNumeric></ix:nonNumeric>**</div>
        </td>

  </tr>

  <tr>

    <td style="width: 15.11%; vertical-align: top; background-color: #CCEEFF;">
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="ecd:TrdArrIndTitle" id="Fact_2db293bbcf6e4d2c97282f407aa32968" contextRef="c20240401to20240630_IndividualAxis_BrettMoniaMember">Chief Executive Officer</ix:nonNumeric></div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Termination</div>
        </td>

    <td style="width: 2.54%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10.16%; vertical-align: top; background-color: #CCEEFF;">
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        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 7.98%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="ecd:Rule10b51ArrTrmntdFlag" id="Fact_3a9099e73e3d4b61b04d191d9d21de91" contextRef="c20240401to20240630_IndividualAxis_BrettMoniaMember" format="ixt:fixed-true">X</ix:nonNumeric></div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.24%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;">
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        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 22.1%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_916e87d3015b45708cd1e86a514e8307">Upon the execution of all instructions provided in the plan</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 15.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="ecd:TrdArrIndName" id="Fact_732d98410c54495cb0fa3eb43bfa4d11" contextRef="c20240401to20240630_IndividualAxis_RichardSGearyMember">Richard S. Geary</ix:nonNumeric></div>
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="ecd:TrdArrIndTitle" id="Fact_e120faf416164674966986a85353d842" contextRef="c20240401to20240630_IndividualAxis_RichardSGearyMember">EVP, Chief Development Officer</ix:nonNumeric></div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adoption</div>
        </td>

    <td style="width: 2.54%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10.16%; vertical-align: top; background-color: #FFFFFF;">
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        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 7.98%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="ecd:Rule10b51ArrAdoptedFlag" id="Fact_a8ef4ad9c3a54e529b7bba32bb8fd6d4" contextRef="c20240401to20240630_IndividualAxis_RichardSGearyMember" format="ixt:fixed-true">X</ix:nonNumeric></div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ecd:TrdArrSecuritiesAggAvailAmt" id="Fact_ae09e1a781a54937960ba5f5e9467d30" contextRef="c20240630_IndividualAxis_RichardSGearyMember" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">241,732</ix:nonFraction></div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 22.1%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The earlier to occur of (i) <span style="-sec-ix-hidden:Fact_d6467e3eb7f84e94a4d98fb98d8f059a">July 7, 2025</span>,
            and (ii) Upon the execution of all instructions provided in the plan</div>
        </td>

  </tr>


</table>
</ix:continuation></div>

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

  <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;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">50</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">Index</a></div>

    </div>

  </div>

  <div style="text-align: left;"><a id="ITEM6"><!--Anchor--></a><br/>
  </div>

  <table cellspacing="0" cellpadding="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: 72pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 6.</td>

    <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;">EXHIBITS</div>
        </td>

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</table>
  <div><br/>
  </div>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a.</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exhibits</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

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


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    <td style="width: 8.46%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit Number</div>
        </td>

    <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>

  </tr>

  <tr>

    <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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="ex10-1.htm">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;">Second Amendment dated as of June 11, 2024 to the Amended and Restated Lease Agreement dated as of August 21, 2023 by and between the Registrant and
            Lots 21 and 22 Owner (DE) LLC, a Delaware limited liability company.</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>

  </tr>

  <tr>

    <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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="ex10-2.htm">10.2</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;">Amended and Restated License Agreement by and between the Registrant and Otsuka Pharmaceutical Co., Ltd. dated June 18, 2024. Portions of this
            exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</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>

  </tr>

  <tr>

    <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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="ex31-1.htm">31.1</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;">Certification by Chief Executive Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended.</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>

  </tr>

  <tr>

    <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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="ex31-2.htm">31.2</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;">Certification by Chief Financial Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended.</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>

  </tr>

  <tr>

    <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 style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="ex32-1.htm">32.1</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;">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>

  </tr>

  <tr>

    <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;">101</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;">The following financial statements from the Ionis Pharmaceuticals, Inc. Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, formatted in Inline Extensible Business Reporting Language (iXBRL): (i) condensed consolidated balance sheets, (ii) condensed
            consolidated statements of operations, (iii) condensed consolidated statements of comprehensive income (loss), (iv) condensed consolidated statements of stockholders&#8217; equity, (v) condensed consolidated statements of cash flows and (vi) notes to
            condensed consolidated financial statements (detail tagged).</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>

  </tr>

  <tr>

    <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;">104</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;">Cover Page Interactive Data File (formatted in iXBRL and included in exhibit 101).</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <table cellspacing="0" cellpadding="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; 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;">This certification is deemed not filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liability of that
            section, nor shall it be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended.</div>
        </td>

  </tr>


</table>
  <div><br/>
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-weight: normal; font-style: normal;">51</span></div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <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 style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#Index">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>

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


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    <td style="width: 27.57%; 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;">Signatures</div>
        </td>

    <td style="width: 2.19%; vertical-align: bottom;">&#160;</td>

    <td style="width: 50.36%; 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;">Title</div>
        </td>

    <td style="width: 2.15%; vertical-align: bottom;">&#160;</td>

    <td style="width: 17.72%; 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;">Date</div>
        </td>

  </tr>

  <tr>

    <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>

    <td style="width: 17.72%; vertical-align: top;">&#160;</td>

  </tr>

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    <td style="width: 27.57%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ BRETT P. MONIA</div>
        </td>

    <td style="width: 2.19%; vertical-align: bottom;" rowspan="2">&#160;</td>

    <td style="width: 50.36%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director and Chief Executive Officer</div>
        </td>

    <td style="width: 2.15%; vertical-align: bottom;" rowspan="2">&#160;</td>

    <td style="width: 17.72%; vertical-align: bottom;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 27.57%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia, Ph.D.</div>
        </td>

    <td style="width: 50.36%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Principal executive officer)</div>
        </td>

    <td style="width: 17.72%; vertical-align: bottom;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">August 1, 2024</div>
        </td>

  </tr>

  <tr>

    <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>

    <td style="width: 17.72%; vertical-align: bottom;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 27.57%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ ELIZABETH L. HOUGEN</div>
        </td>

    <td style="width: 2.19%; vertical-align: bottom;" rowspan="2">&#160;</td>

    <td style="width: 50.36%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Finance and Chief Financial Officer</div>
        </td>

    <td style="width: 2.15%; vertical-align: bottom;" rowspan="2">&#160;</td>

    <td style="width: 17.72%; vertical-align: bottom;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 27.57%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elizabeth L. Hougen</div>
        </td>

    <td style="width: 50.36%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Principal financial and accounting officer)</div>
        </td>

    <td style="width: 17.72%; vertical-align: bottom;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">August 1, 2024</div>
        </td>

  </tr>


</table>
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  </div>

  <div style="text-align: center;"><span style="font-size: 8pt;">52</span><br/>
  </div>

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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>
      <div style="text-align: right;"><a name="z_Hlk168581603"></a>Exhibit 10.1</div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;"><u>SECOND AMENDMENT TO AMENDED AND RESTATED LEASE</u></div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">This SECOND AMENDMENT TO AMENDED AND RESTATED LEASE (&#8220;<font style="font-weight: bold;">Amendment</font>&#8221;) is made as of June 11, 2024 (the &#8220;<font style="font-weight: bold;">Effective Date</font>&#8221;),
        by and between LOTS 21 &amp; 22 OWNER (DE) LLC, a Delaware limited liability company (&#8220;<font style="font-weight: bold;">Landlord</font>&#8221;), and IONIS PHARMACEUTICALS, INC., a Delaware corporation (&#8220;<font style="font-weight: bold;">Tenant</font>&#8221;).</div>
      <div>&#160;</div>
      <div style="text-align: center; font-size: 12pt;"><font style="font-size: 10pt;"><u>R E C I T A L S</u>:</font></div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">A.&#160;&#160;&#160;&#160; &#160; &#160; Landlord and Tenant are parties to that certain Amended and Restated Lease Agreement dated as of August 21, 2023, as amended by that certain First Amendment to Amended and Restated Lease
        dated as of November 6, 2023 (together, the &#8220;<font style="font-weight: bold;">Lease</font>&#8221;), pursuant to which Tenant leases from Landlord certain Premises that include certain Land, a Building under construction containing approximately 164,757
        rentable square feet in the aggregate, and certain other improvements, all as more particularly described in the Lease.</div>
      <div>&#160; <br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">C.&#160;&#160;&#160; &#160;&#160; &#160; Tenant desires to commence the construction of its Tenant Improvements earlier than originally anticipated and Landlord and Tenant have agreed to modify the scope of work necessary for
        Delivery Condition to occur for the purposes of facilitating the same.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">D.&#160;&#160;&#160;&#160;&#160; &#160;&#160; The parties desire to amend the Lease in order to amend, among other things, the definition of Delivery Condition and certain matters related thereto.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">D.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Capitalized terms not defined herein have the meanings given to such terms in the Lease.</div>
      <div>&#160;</div>
      <div style="text-align: center; font-size: 12pt;"><font style="font-size: 10pt;"><u>W </u><u>I</u>&#160;<u>T N E S S E T H</u>:</font></div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">NOW, THEREFORE, in consideration of the above Recitals and other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the parties agree as follows:</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">The Lease is hereby amended as follows:</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">1.&#160;&#160;&#160;&#160; &#160;&#160; &#160; <u>Delivery Condition</u>.&#160; Schedule 7 to Exhibit B to the Lease is hereby deleted and replaced in its entirety by <u>Schedule 7</u> attached to this Amendment.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">2.&#160;&#160;&#160;&#160;&#160; &#160;&#160;&#160; <u>Estimated Calculation Notice</u>. Section 2.1.2 of the Lease is hereby amended by deleting the words &#8220;one hundred eighty (180)&#8221; in the first line thereof and inserting the words
        &#8220;two hundred seventy (270)&#8221; in their place.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">3.&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; <u>Delivery Date</u>. Within Section 3.1 of the Work Letter, Exhibit B to the Lease, the definition of Delivery Date is hereby deleted and replaced in its entirety with the following:</div>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">Page 1</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
      </div>
      <div style="text-align: justify;">&#8220;As used herein, the &#8220;<font style="font-weight: bold;">Delivery Date</font>&#8221; means the date&#160; that is the earlier to occur of (x) the date (i) the Landlord&#8217;s Construction Work is in the condition required by Schedule
        7 (the &#8220;<font style="font-weight: bold;">Delivery Condition</font>&#8221;), and (ii) Landlord has provided Tenant with reasonably continuous and uninterrupted access to the Project for the construction of Tenant Improvements, subject to the reasonable
        requirements necessary for, and established by, Landlord's General Contractor to allow it to achieve Substantial Completion, complete the Punchlist Items and exercise any of its other rights or obligations under this Work Letter and the Lease
        within the time periods set forth herein, and (y) sixty (60) days after the date that Tenant enters any portion of the Premises for the commencement of substantial work in connection with the Tenant Improvements; provided, however, in no event
        shall minor work such as the MEP deck inserts/hangers or other minor work that is installed early in the interest of efficiency be considered the commencement of the Tenant Improvements, and in no event shall the Delivery Date be any earlier than
        November 6, 2024.&#8221;</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">4.&#160;&#160;&#160;&#160;&#160; &#160;&#160; <u>Construction of the Tenant Improvements and LCW by Tenant; Coordination</u>. Section 6.4(a) of the Work Letter, Exhibit B to the Lease, is hereby amended by deleting within the third
        paragraph the words &#8220;the first day of the 18<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> month&#8221; and inserting the words &#8220;the first day of the 21<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">st</sup> month&#8221; in their place.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">5.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Successors and Assigns</u>.&#160; Subject to the provisions of <u>Article 5 of the Lease</u>, the provisions of the Lease, as affected by this Amendment, shall be binding upon and inure
        to the benefit of the heirs, successors, executors, administrators, and assigns of Landlord and Tenant.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">6.&#160;&#160;&#160;&#160;&#160; &#160;&#160;&#160; <u>Tenant Improvement Allowance; Funding of TI by LL</u>. The last sentence of the first paragraph of Section 10.2(a) of the Work Letter, Exhibit B to the Lease, is hereby amended and
        restated in its entirety as follows:</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">&#8220;Landlord shall have no obligation to make any disbursements of TI Allowance not properly requisitioned by Tenant by the date that is one year following the Commencement Date and Tenant shall have
        no further right to any undisbursed TI Allowance thereafter; provided that the portion of the TI Allowance not requisitioned by Tenant with respect to the Day 1 Space may be requisitioned by Tenant for the Day 2 Space by the date that is 21 months
        following the Commencement Date, and, thereafter, Tenant shall have no further right to any undisbursed TI Allowance.&#8221;</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">7.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Submission</u>. The submission of this Amendment to Tenant or a summary of some or all of its provisions for examination does not constitute a reservation of or option to amend the
        Lease as set forth herein until fully executed by Tenant and Landlord.&#160; Landlord represents that this Amendment has been&#160; approved by the holder of any mortgage or deed of trust covering the Land having the right to approve this Amendment.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">8.&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Authority</u>. Tenant warrants and represents that (a) Tenant is duly organized, validly existing and in good standing under the laws of the jurisdiction in which such entity was
        organized; (b) Tenant has duly executed and delivered this Amendment; (c) the execution, delivery and performance by Tenant of this Amendment (i) are within the powers of Tenant, (ii) have been duly authorized by all requisite action (subject to
        the immediately following paragraph), (iii) will not violate any provision of law or any order of any court or agency of government, or any agreement or other instrument to which Tenant is a party or by which it or any of its property is bound, and
        (iv) will not result in the imposition of any lien or charge on any of Tenant&#8217;s property, except by the provisions of this Amendment; and (d) this Amendment is a valid and binding obligation of Tenant in accordance with its terms.</div>
      <div>&#160;</div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">Page 2</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">Landlord warrants and represents that (a) Landlord is duly organized, validly existing and in good standing under the laws of the jurisdiction in which such entity was organized; (b)&#160; Landlord has
        duly executed and delivered this Amendment; (c) the execution, delivery and performance by Landlord of this Amendment (i) are within the powers of Landlord, (ii) have been duly authorized on behalf of Landlord by all requisite action and (iii) will
        not violate any provision of law or any order of any court or agency of government, or any agreement or other instrument to which Landlord is a party or by which it or any of its property is bound; and (d) this Amendment is a valid and binding
        obligation of Landlord in accordance with its terms.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">9.&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; <u>No Other Modifications</u>.&#160; Except as modified in this Amendment, all other terms and conditions of the Lease shall remain unchanged and in full force and effect.&#160; As amended by
        this Amendment, the Lease represents the entire agreement between the parties with respect to the matters set forth herein. To the extent of a conflict between the terms of the Lease and this Amendment, this Amendment shall prevail.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">10.&#160;&#160;&#160;&#160; &#160;&#160; <u>Counterparts</u>. This Amendment may be executed in 2 or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same
        instrument.&#160; Counterparts may be delivered via facsimile, electronic mail (including pdf or any electronic signature process complying with the U.S. federal ESIGN Act of 2000) or other transmission method and any counterpart so delivered shall be
        deemed to have been duly and validly delivered and be valid and effective for all purposes.&#160; Electronic signatures shall be deemed original signatures for purposes of this Amendment and all matters related thereto, with such electronic signatures
        having the same legal effect as original signatures.</div>
      <div>&#160;</div>
      <div style="text-align: center;">[SIGNATURES ON FOLLOWING PAGES]</div>
      <div style="text-align: center;"> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">Page 3</font></div>
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          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">IN WITNESS WHEREOF</font><font style="font-size: 10pt;">, the parties hereto have duly executed this Amendment on the day and year
          first above written.</font></div>
      <div>&#160;</div>
      <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;" id="zdd3c813766bb46d6b2e399f03814a302">

          <tr>
            <td rowspan="1" style="width: 50%; vertical-align: top;">
              <div style="font-weight: bold;">LANDLORD:</div>
            </td>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 50%; vertical-align: top;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">LOTS 21 &amp; 22 OWNER (DE) LLC, </font><font style="font-size: 10pt;">a Delaware </font></div>
            </td>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 50%; vertical-align: top;">
              <div style="font-size: 12pt;"><font style="font-size: 10pt;">limited liability company</font></div>
            </td>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 50%; vertical-align: top;">
              <div>By: <u>/s/Tycho Suter</u></div>
            </td>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 50%; vertical-align: top;">
              <div>Name: <u>Tycho Suter</u></div>
            </td>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 50%; vertical-align: top;">
              <div>Title: <u>Vice President</u></div>
            </td>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 50%; vertical-align: top;">
              <div>By: <u>/s/Kristen Binck</u></div>
            </td>
            <td rowspan="1" style="width: 50%; vertical-align: top;"><br>
            </td>
          </tr>
          <tr>
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              <div>Name: <u>Kristen Binck</u></div>
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          <tr>
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              <div style="font-weight: bold;">TENANT:</div>
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          <tr>
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              <div style="font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC., </font><font style="font-size: 10pt;">a </font></div>
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          <tr>
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              <div style="font-size: 12pt;"><font style="font-size: 10pt;">Delaware corporation</font></div>
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              <div>By: <u>/s/Beth Hougen</u></div>
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              <div>Name: <u>Beth Hougen</u></div>
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      <div>&#160;</div>
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              <div>The following is not required for the achievement of Delivery Condition but Landlord shall continue diligently and continuously, subject to Sections 7 and 12 of the Work Letter, following Delivery Condition, to use good faith, diligent
                efforts to prosecute the same, estimated for completion by February 21, 2025: the Building becomes &#8220;dried in&#8221; meaning that it is a &#8220;water tight shell&#8221;, whether by permanent or temporary measures,<a name="z_cp_change_5"></a> in a manner that
                Landlord reasonably determines in good faith, based on the input of General Contractor, will not interfere with the progress of the Tenant Improvements in any material way due to the condition of the Building exterior.</div>
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      <div>&#160;</div>
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              <div>As part of Tenant&#8217;s schematic document submission to Landlord for the Tenant Improvements, Tenant shall identify any locations (not to exceed a reasonable number) where Tenant desires to place deck inserts on each floor of the Premises
                to accommodate Tenant&#8217;s internal staircases or similar, customary items consistent with comparable first-class buildings used for life sciences purposes. Landlord shall cooperate and collaborate with Tenant to allow for the installation of
                such approved deck inserts, if any, prior to the occurrence of Delivery Condition, subject to agreeing with Tenant on the minimum amount of Tenant Delay resulting from the same and the other terms and conditions of the Work Letter.</div>
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              <div>Installation of floors should be sufficiently complete to allow layout to begin of floor surfaces, column lines, control lines or (to the extent applicable) Trimble reference points.&#160; Any stored material for Landlord&#8217;s Construction Work
                (including turnover attic stock) must be located outside of the building (on site), or in an area or areas on each applicable floor designated by the General Contractor that permit the orderly progress of Tenant Improvements.</div>
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      <div>&#160;</div>
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              <div>Site access is available, as reasonably designated by the General Contractor, for efficient material delivery and Building loading.</div>
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      <div>&#160;</div>
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              <div>Site access is available for the Tenant Improvement contractor and subcontractor&#8217;s construction trailer (if applicable) and laydown space in a location reasonably designated by the General Contractor.</div>
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      <div>&#160;</div>
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            <td style="width: 18pt; vertical-align: top;"><a name="z_cp_change_8"></a>7.</td>
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              <div>Temporary electrical <a name="z_cp_change_10"></a>infrastructure is available to the Premises and Building, with sufficient capacity to power small tools, temporary lighting, and equipment to provide temporary ventilation/heating to
                perform the Tenant Improvements using normal means of power use.</div>
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              <div>The following is not required for the achievement of Delivery Condition but Landlord shall continue diligently and continuously, subject to Sections 7 and 12 of the Work Letter, following Delivery Condition, to use good faith, diligent
                efforts to&#160; prosecute the same, for completion by April 23<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">rd</sup>, 2025: Tenant&#8217;s Contractor has ability to terminate electrical wires in electrical switchgear and distribution boards installed as part of the Landlord&#8217;s Construction
                Work.</div>
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              <div>Tenant&#8217;s contractor is able to use fire stairs to travel to and from the street level and between each Tenant floor by either permanent or temporary means.&#160; Use of stairs subject to coordination with Landlord&#8217;s completion of finishes and
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<DOCUMENT>
<TYPE>EX-10.2
<SEQUENCE>3
<FILENAME>ex10-2.htm
<DESCRIPTION>EXHIBIT 10.2
<TEXT>
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                <div style="text-align: justify; font-style: italic; font-weight: bold;">CONFIDENTIAL</div>
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              <td style="width: 50%; vertical-align: top;">
                <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
              </td>
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      <div style="text-align: right; font-weight: bold;"> <br>
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      <div style="text-align: right; font-weight: bold;">Exhibit 10.2</div>
      <div>&#160;</div>
      <div style="text-align: center; color: rgb(0, 0, 0);">Certain portions of this exhibit, marked by [***], have been excluded because they are both not material and are the type that the registrant treats as private or confidential.</div>
      <div>&#160;</div>
      <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Amended and Restated License Agreement</div>
      <div>&#160;</div>
      <div style="text-align: center; font-variant: small-caps; font-weight: bold;">By and Between</div>
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      <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
      <div>&#160;</div>
      <div style="text-align: center; font-variant: small-caps; font-weight: bold;">and</div>
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      <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Otsuka Pharmaceutical Co., Ltd.</div>
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      <div style="text-align: center; font-weight: bold;">Dated June 18, 2024</div>
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        <div style="text-align: justify; font-style: italic; font-weight: bold;">CONFIDENTIAL</div>
        <div style="text-align: justify; font-style: italic; font-weight: bold;"> <br>
        </div>
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              <div style="text-align: center; font-weight: bold;">TABLE OF CONTENTS</div>
            </td>
          </tr>
          <tr>
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            <td rowspan="1" colspan="3" style="vertical-align: top;">&#160;</td>
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              <div style="margin-right: 36pt;">ARTICLE 1 OVERVIEW</div>
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            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">1</div>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>1.1</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Development and Commercialization</div>
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            <td style="width: 10%; vertical-align: top; text-align: right;">1</td>
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          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>1.2</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Governance</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">2</div>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>1.3</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Purpose</div>
            </td>
            <td style="width: 10%; vertical-align: top;">
              <div style="text-align: right;">2</div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
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            <td rowspan="1" style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
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              <div style="margin-right: 36pt;">ARTICLE 2 LICENSES</div>
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              <div style="text-align: right;">2</div>
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            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>2.1</div>
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            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>License Grants to Otsuka</div>
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            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">2</div>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>2.2</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>License Grant to Ionis</div>
            </td>
            <td style="width: 10%; vertical-align: top;">
              <div style="text-align: right;">2</div>
            </td>
          </tr>
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            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
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            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>2.3</div>
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            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Sublicensing and Subcontracting Terms</div>
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            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">3</div>
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            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
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            <td style="width: 7%; vertical-align: top;">
              <div>2.4</div>
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            <td style="width: 77%; vertical-align: top;">
              <div>Collaboration Technology Enabling License</div>
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            <td style="width: 10%; vertical-align: top;">
              <div style="text-align: right;">3</div>
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              <div>2.5</div>
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            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>No Other Rights and Retained Rights; Negative Covenant</div>
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            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">4</div>
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            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
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            <td style="width: 7%; vertical-align: top;">
              <div>2.6</div>
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            <td style="width: 77%; vertical-align: top;">
              <div>Existing Third-Party IP Agreements</div>
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            <td style="width: 10%; vertical-align: top;">
              <div style="text-align: right;">4</div>
            </td>
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          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
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            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>2.7</div>
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            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>New Third-Party IP Agreements</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">5</div>
            </td>
          </tr>
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            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>2.8</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Right of First Negotiation for Follow-On Products</div>
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            <td style="width: 10%; vertical-align: top;">
              <div style="text-align: right;">6</div>
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            <td rowspan="1" style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
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              <div style="margin-right: 36pt;">ARTICLE 3 TECHNOLOGY TRANSFER</div>
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              <div style="text-align: right;">8</div>
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              <div>3.1</div>
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            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Initial Know-How Transfer</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">8</div>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>3.2</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Technology Transfer Costs</div>
            </td>
            <td style="width: 10%; vertical-align: top;">
              <div style="text-align: right;">8</div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td rowspan="1" style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; width: 6%;" rowspan="1">
              <div style="margin-right: 36pt;">ARTICLE 4 DEVELOPMENT</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">8</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>4.1</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Development Diligence Obligations</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">8</div>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>4.2</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Development Plans</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">9</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>4.3</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Otsuka Territory-Specific Development Plans</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">10</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>4.4</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Development Costs</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">12</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>4.5</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Development Reports</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">16</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>4.6</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Development Records; Cooperation</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">16</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>4.7</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Data Transfer</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">17</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td rowspan="1" style="width: 7%; vertical-align: top;">&#160;</td>
            <td rowspan="1" style="width: 77%; vertical-align: top;">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; text-align: right;">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; background-color: rgb(204, 238, 255); width: 6%;" rowspan="1">
              <div style="margin-right: 36pt;">ARTICLE 5 REGULATORY AFFAIRS</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">17</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>5.1</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Regulatory Responsible Party</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">17</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>5.2</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Europe Regulatory Subcommittee</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">17</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>5.3</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Correspondences with Regulatory Authorities</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">18</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>5.4</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Regulatory Meetings</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">18</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>5.5</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Regulatory Submissions</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">18</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>5.6</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Cooperation</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">18</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>5.7</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Cost of Regulatory Activities</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">19</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>5.8</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>No Harmful Actions</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">19</td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">2</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zf9121ed144cf4c9886a50ebe98ac636a">

          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>5.9</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Right of Reference</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">19</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>5.10</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Pharmacovigilance; Safety Information</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">20</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>5.11</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Pharmacovigilance Subcommittee</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">20</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>5.12</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Ionis Internal Oligonucleotide Safety Database</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">21</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>5.13</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Recall, Withdrawal, or Field Alerts</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">21</td>
          </tr>
          <tr>
            <td rowspan="1" colspan="1" style="vertical-align: top; width: 6%;"><br>
            </td>
            <td rowspan="1" colspan="2" style="vertical-align: top;">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; background-color: rgb(204, 238, 255); width: 6%;" rowspan="1">
              <div>ARTICLE 6 COMMERCIALIZATION AND MEDICAL AFFAIRS</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">22</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>6.1</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Commercialization Responsibilities for Licensed Product</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">22</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>6.2</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Commercialization and Medical Affairs Reporting</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">22</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>6.3</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Pricing</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">23</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>6.4</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Brand Strategy and Operating Plans.</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">23</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>6.5</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Otsuka Commercialization Diligence Obligation</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">24</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>6.6</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Medical Affairs Plans.</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">24</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>6.7</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Standards of Conduct; Compliance</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">25</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>6.8</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Product Materials</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">25</div>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>6.9</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Diversion</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">26</td>
          </tr>
          <tr>
            <td rowspan="1" colspan="1" style="vertical-align: top; background-color: rgb(204, 238, 255); width: 6%;"><br>
            </td>
            <td rowspan="1" colspan="2" style="vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; width: 6%;" rowspan="1">
              <div>ARTICLE 7 MANUFACTURING</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">26</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>7.1</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Responsibility</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">26</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>7.2</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Supply and Quality Agreements; Manufacturing Costs</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">27</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>7.3</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Audits and Inspections</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">28</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>7.4</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Manufacturing Technology Transfer</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">29</td>
          </tr>
          <tr>
            <td rowspan="1" colspan="1" style="vertical-align: top; background-color: rgb(204, 238, 255); width: 6%;"><br>
            </td>
            <td rowspan="1" colspan="2" style="vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; width: 6%;" rowspan="1">
              <div>ARTICLE 8 GOVERNANCE</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">29</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>8.1</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Executive Committee.</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">29</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>8.2</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Joint Steering Committees</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">30</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>8.3</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Subcommittees</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">34</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>8.4</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Additional Participants</div>
            </td>
            <td style="width: 10%; vertical-align: top;">
              <div style="text-align: right;">35</div>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>8.5</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Decision-Making</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">35</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>8.6</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Resolution of Committee Disputes</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">36</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>8.7</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Day-to-Day Responsibilities</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">37</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>8.8</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Alliance Manager</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">37</td>
          </tr>
          <tr>
            <td rowspan="1" colspan="1" style="vertical-align: top; background-color: rgb(204, 238, 255); width: 6%;"><br>
            </td>
            <td rowspan="1" colspan="2" style="vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; width: 6%;" rowspan="1">
              <div>ARTICLE 9 PAYMENTS</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">37</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>9.1</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Upfront Payment</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">37</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>9.2</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Milestone Payments</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">37</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>9.3</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Royalties</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">39</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>9.4</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Other Amounts Payable</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">42</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>9.5</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Financial Records and Audits</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">42</td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">3</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zc91af67838c84f9590336f805f509d2e">

          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>9.6</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>No Refunds</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">42</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>9.7</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Accounting Standards</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">42</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>9.8</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Method of Payment; Exchange Rate</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">43</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>9.9</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Blocked Payments</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">43</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>9.10</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Taxes</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">43</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>9.11</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Late Payments; Disputed Payments</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">44</td>
          </tr>
          <tr>
            <td rowspan="1" colspan="1" style="vertical-align: top; background-color: rgb(204, 238, 255); width: 6%;"><br>
            </td>
            <td rowspan="1" colspan="2" style="vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; width: 6%;" rowspan="1">
              <div>ARTICLE 10 INTELLECTUAL PROPERTY</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">44</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>10.1</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Inventions</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">44</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>10.2</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Patent Prosecution</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">46</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>10.3</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Enforcement Against Third Party Infringement or Misappropriation</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">48</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>10.4</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Defense of Third-Party Patent Challenges</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">49</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>10.5</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Third Party Infringement Claims</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">51</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>10.6</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Patent Challenges of Third-Party Patent Rights</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">51</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>10.7</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Patent Term Extensions</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">52</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>10.8</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Unified Patent Court;</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">52</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>10.9</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Common Interest</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);">53</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>10.10</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Product Trademarks</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">53</td>
          </tr>
          <tr>
            <td rowspan="1" colspan="1" style="vertical-align: top; background-color: rgb(204, 238, 255); width: 6%;"><br>
            </td>
            <td rowspan="1" colspan="2" style="vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; width: 6%;" rowspan="1">
              <div>ARTICLE 11 REPRESENTATIONS, WARRANTIES, AND COVENANTS</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">57</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>11.1</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Mutual Representations and Warranties</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">57</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>11.2</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Additional Ionis Representations and Warranties</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">57</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>11.3</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Additional Representations and Warranties</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">60</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>11.4</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Additional Covenants</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">60</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>11.5</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Disclaimer</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">61</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>11.6</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Limitation of Liability</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">61</td>
          </tr>
          <tr>
            <td rowspan="1" colspan="1" style="vertical-align: top; background-color: rgb(204, 238, 255); width: 6%;"><br>
            </td>
            <td rowspan="1" colspan="2" style="vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; width: 6%;" rowspan="1">
              <div>ARTICLE 12 CONFIDENTIALITY</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">62</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>12.1</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Duty of Confidence</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">62</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>12.2</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Confidential Information</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">62<br>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>12.3</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Exemptions</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">63</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>12.4</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Authorized Disclosures</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">63</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>12.5</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Publications</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">65</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>12.6</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Publicity; Use of Names</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">65</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>12.7</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Acknowledgement</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">66</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td rowspan="1" style="width: 7%; vertical-align: top;">&#160;</td>
            <td rowspan="1" style="width: 77%; vertical-align: top;">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; text-align: right;">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; background-color: rgb(204, 238, 255); width: 6%;" rowspan="1">
              <div>ARTICLE 13 INDEMNIFICATION</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">67</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>13.1</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Indemnification by Ionis</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">67</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>13.2</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Indemnification by Otsuka</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">67</td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">4</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <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;" id="z592cee40756b41b6818c59e5918e056e">

          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>13.3</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Indemnification Procedure</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">67</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>13.4</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Insurance</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">68</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td rowspan="1" style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; width: 6%;" rowspan="1">
              <div>ARTICLE 14 TERM AND TERMINATION</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">68</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>14.1</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Term</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">68</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>14.2</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Termination for Material Breach</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">68</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>14.3</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Termination by Otsuka for Convenience</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">69</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>14.4</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Discontinuation of Development and Commercialization</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">69</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>14.5</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Termination For Patent Challenge</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">69<br>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>14.6</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Termination for Insolvency</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">70</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>14.7</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Rights in Bankruptcy</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">70</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>14.8</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Full Force and Effect During Notice Period</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">70</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>14.9</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Effects of Termination</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">70</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>14.10</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Survival; Accrued Rights</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">75</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td rowspan="1" style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; width: 6%;" rowspan="1">
              <div>ARTICLE 15 DISPUTE RESOLUTION; GOVERNING LAW</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">76</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>15.1</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Executive Officers; Disputes</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">76</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>15.2</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Arbitration</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">76</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>15.3</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Intellectual Property Disputes</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">77</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>15.4</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Equitable Remedies</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">77</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>15.5</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Governing Law; English Language</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">77</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td rowspan="1" style="width: 7%; vertical-align: top;">&#160;</td>
            <td rowspan="1" style="width: 77%; vertical-align: top;">&#160;</td>
            <td rowspan="1" style="width: 10%; vertical-align: top; text-align: right;">&#160;</td>
          </tr>
          <tr>
            <td colspan="3" style="vertical-align: top; background-color: rgb(204, 238, 255); width: 6%;" rowspan="1">
              <div>ARTICLE 16 MISCELLANEOUS</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">78</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>16.1</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Assignment</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">78</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>16.2</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Entire Agreement; Amendment</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">78<br>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>16.3</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>No Strict Construction; Interpretation</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">79<br>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>16.4</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Severability</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">80<br>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>16.5</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Force Majeure</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">80</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>16.6</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Notices</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">80</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>16.7</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Further Assurances</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">81</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>16.8</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Performance by Affiliates</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">81</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>16.9</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Agency</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">81</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>16.10</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Binding Effect; No Third-Party Beneficiaries or Obligors</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">82</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>16.11</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>No Waiver</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">82</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>16.12</div>
            </td>
            <td style="width: 77%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Cumulative Remedies</div>
            </td>
            <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">82</td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;" colspan="1"><br>
            </td>
            <td style="width: 7%; vertical-align: top;">
              <div>16.13</div>
            </td>
            <td style="width: 77%; vertical-align: top;">
              <div>Counterparts</div>
            </td>
            <td style="width: 10%; vertical-align: top; text-align: right;">82<br>
            </td>
          </tr>

      </table>
      <div style="text-align: justify;"><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">5</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
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      <!--PROfilePageNumberReset%Num%1%%%-->
      <div style="text-align: center; font-weight: bold;">AMENDED AND RESTATED LICENSE AGREEMENT</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">This <font style="font-weight: bold; font-variant: small-caps;">Amended and Restated License Agreement</font><font style="font-weight: bold;">&#160;</font>(this &#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;) is made and entered into as of June 18, 2024 (the &#8220;<font style="font-weight: bold; font-style: italic;">Restatement Date</font>&#8221;) between <font style="font-weight: bold; font-variant: small-caps;">Ionis
          Pharmaceuticals, Inc.</font>, a Delaware corporation, having its principal place of business at 2855 Gazelle Court, Carlsbad CA 92010 USA (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;), and <font style="font-weight: bold; font-variant: small-caps;">Otsuka Pharmaceutical Co., Ltd.</font>, a company organized and existing under the laws of Japan, having a place of business at 2-9, Kanda Tsukasa-machi, Chiyoda-ku, Tokyo 101-8535, Japan (&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka</font>&#8221;). Ionis and Otsuka may be referred to in this Agreement individually as a &#8220;<font style="font-weight: bold; font-style: italic;">Party</font>&#8221; and collectively as the &#8220;<font style="font-weight: bold; font-style: italic;">Parties</font>.&#8221; Capitalized terms used in this Agreement, whether used in the singular or the plural, have the meaning set forth in <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 1</u> (Definitions). All
        attached appendices and schedules are a part of this Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">RECITALS</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">WHEREAS</font>, Ionis possesses certain Patent Rights, Know-How, technology and expertise with respect to research, development, and manufacturing of drugs for the
        treatment of HAE, and has regulatory and commercial capabilities in the Ionis Territory;</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">WHEREAS</font>, Otsuka (itself and through its Affiliates) has expertise in the development and commercialization of biopharmaceutical products and has regulatory,
        development, and commercial capabilities in the Otsuka Territory;</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">WHEREAS</font>, Ionis and Otsuka entered into that certain License Agreement, dated as of December 15, 2023 (the &#8220;<font style="font-weight: bold; font-style: italic;">Original Effective Date</font>&#8221; and such License Agreement, the &#8220;<font style="font-weight: bold; font-style: italic;">Original Agreement</font>&#8221;) for the Development and Commercialization of the Licensed Products in the Europe Territory,
        as set forth in, and subject to the terms of, the Original Agreement;</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">WHEREAS</font>, the Original Agreement will continue to govern the Parties&#8217; rights and obligations during the Original Agreement Term; and</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">WHEREAS</font>, the Parties desire to amend and restate the Original Agreement from and after the Restatement Date in order to, among other things, expand Otsuka&#8217;s
        rights to Develop and Commercialize the Licensed Products in the Asia Territory in addition to the Europe Territory, as set forth in, and subject to the terms of, this Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">NOW THEREFORE</font>, the Parties agree as follows:</div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">ARTICLE 1</div>
      <div style="text-align: center; font-weight: bold;">OVERVIEW</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6dfeb238115c4500a867999c02f48bdf">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Development and Commercialization</font>. As of the Restatement Date, Ionis is Developing a Licensed Product in ongoing Clinical Trials in both the Europe Territory and the Ionis Territory (such studies,
                as further described and defined in <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan)). Under this Agreement, the Parties intend (a) that Ionis will continue to conduct the Ongoing Cross-Territory Studies in accordance with
                the Cross-Territory Clinical Development Plan, at [***] and (b) to share the costs of all Future Cross-Territory Studies included in the Cross-Territory Clinical Development Plan as of the Original Effective Date and any additional
                Cross-Territory Clinical Studies included in any updated version of the Cross-Territory Clinical Development Plan approved by the [***], in each case, in accordance with the [***]. In addition, the Parties intend for Ionis to Commercialize
                the Licensed Products in the Ionis Territory and Otsuka to Commercialize the Licensed Products in the Otsuka Territory, which Commercialization activities will be consistent with the global commercialization and global medical affairs
                strategy (as further described in <u>Article 6</u> (Commercialization and Medical Affairs)).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">1</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <!--PROfilePageNumberReset%Num%2%%%-->
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7532c2ea439a4cbc8d92f572bfa28a65">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Governance</font>. The Parties have agreed to form a Europe joint steering committee and an Asia joint steering committee to oversee and coordinate the Development, Manufacturing, and Commercialization
                activities with respect to the Licensed Products under this Agreement in the Europe Territory and Asia Territory, respectively, and an executive committee to resolve matters that are subject to approval, but are not unanimously agreed, by
                such joint steering committees or other Subcommittees.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd95d6444e7dd4c37a90dae6af9fe4551">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Purpose</font>. The purpose of this <u>Article 1</u> (Overview) is to provide a high-level overview of the roles, responsibilities, rights, and obligations of each Party under this Agreement, and
                therefore, this <u>Article 1</u> (Overview) is qualified in its entirety by the more detailed provisions of this Agreement set forth below.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">ARTICLE 2</div>
      <div style="text-align: center; font-weight: bold;">LICENSES</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0629aeb32e244723b465b7efb040f4e6">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">License Grants to Otsuka</font>. Subject to the terms of this Agreement (including Ionis&#8217; retained rights set forth in <u>Section 2.5</u> (No Other Rights and Retained Rights; Negative Covenant)), Ionis
                hereby grants to Otsuka:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9da724289b754fd0b8dcb62261075bb9">

          <tr>
            <td style="width: 36pt;">&#160;</td>
            <td style="width: 36pt; vertical-align: top;">2.1.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>an exclusive, royalty-bearing license, with the right to grant sublicenses solely in accordance with <u>Section 2.3.1(a)</u> (Rights of Otsuka to Grant Sublicenses), under the Ionis Technology and the Unitary Product Trademarks, in each
                case, to (a) Develop the Licensed Products in the Field in the Otsuka Territory in accordance with the Otsuka Territory-Specific Development Plans solely for Commercialization and for the conduct of Medical Affairs for such Licensed
                Products in the Field in the Otsuka Territory and (b) Commercialize and conduct Medical Affairs for the Licensed Products in the Field in the Otsuka Territory. For clarity, the license grants under this <u>Section 2.1.1</u> (License Grants
                to Otsuka) do not include the right to Manufacture the Licensed Products.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zbcd7eeaae36144858a9b8feca81d8e82">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.1.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>a non-exclusive, royalty-bearing license, with the right to grant sublicenses solely in accordance with <u>Section 2.3.1(b)</u> (Rights of Otsuka to Grant Sublicenses), under the Ionis Technology and the Unitary Product Trademarks
                solely to (a) Package and Label the Licensed Products in the Field in the Territory and (b) Manufacture the Licensed Products in the Field in the Territory from and after the time Otsuka provides a Manufacturing Handover Notice, in each
                case ((a) and (b)), solely for Commercialization and for the conduct of Medical Affairs for such Licensed Products in the Field in the Otsuka Territory.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z53bb62323f474ee7b94992d58ab4f03b">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">License Grant to Ionis</font>. Subject to the terms of this Agreement, including Otsuka&#8217;s retained rights set forth in <u>Section 2.5</u> (No Other Rights and Retained Rights; Negative Covenants), Otsuka
                hereby grants to Ionis an exclusive, royalty-free, fully-paid, perpetual license, with the right to grant sublicenses through multiple tiers, under the Otsuka Technology solely to (a) Develop the Licensed Products in the Ionis Territory and
                the Otsuka Territory; <font style="font-style: italic;">provided</font> that, unless this Agreement has been terminated, any such Development in the Otsuka Territory will be conducted solely in accordance with the Cross-Territory Clinical
                Development Plan and the Non-Clinical HAE Development Plans, (b) Manufacture the Licensed Products worldwide in accordance with this Agreement, and (c) Commercialize the Licensed Products in the Ionis Territory in accordance with this
                Agreement and, subject to <u>Section 14.9.5</u> (Sublicenses), worldwide following any termination of this Agreement.&#160; </div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">2</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6b7821766130459793c08f7f3695f1b0">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Sublicensing and Subcontracting Terms</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb172a05c37be4ecaa85123c4db45f1ab">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.3.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Rights of Otsuka to Grant Sublicenses</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z91a1582437c943e483774dc88e3a21bf">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Subject to the terms of this Agreement, Otsuka will have the right to grant sublicenses of the rights granted under <u>Section 2.1.1</u> (License Grants to Otsuka) (i) [***], and (ii) [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4894372313ed4d22a15a83e2edc13537">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Subject to the terms of this Agreement, Otsuka will have the right to grant sublicenses of the rights granted under <u>Section 2.1.2</u> (License Grants to Otsuka) (i) [***], and (ii) [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za9017a12f7db45e6bbac3ef967f5136d">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.3.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Right to Subcontract</font>. Each Party may engage one or more Third Party subcontractors to perform services in furtherance of the performance of its obligations or exercise of its rights under this
                Agreement, including any Third Party contract manufacturer, contract research organization, contract sales organization, wholesaler or distributor (including a distributor that is engaged to conduct promotional activities with respect to
                the Licensed Products on such Party&#8217;s behalf and under such Party&#8217;s control) (&#8220;<font style="font-weight: bold; font-style: italic;">Subcontractors</font>&#8221;); <font style="font-style: italic;">provided </font>that (a) neither Party will
                engage any such Subcontractor that has been Debarred/Excluded; and (b) no engagement of any such Subcontractors will relieve the engaging Party of its obligations under this Agreement or any liability hereunder.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8b01562d07a14c5386b6181c7d07e054">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.3.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Sublicense and Subcontract Agreements</font>. Each agreement pursuant to which a sublicense is granted to a Sublicensee by Otsuka pursuant to this <u>Section 2.3</u> (Sublicensing and Subcontracting
                Terms), each agreement pursuant to which a sublicense is granted to a Sublicensee by Ionis of the rights granted to it under <u>Section 2.2</u> (License Grant to Ionis), and each agreement pursuant to which a Party engages any
                Subcontractor, in each case after the Restatement Date and during the Term, will (a) be subject and subordinate to this Agreement, (b) be consistent with the terms of this Agreement, (c) include obligations of confidentiality and non-use
                applicable to the Confidential Information of the other Party that are at least as stringent as those set forth in <u>Article 12</u> (Confidentiality), and (d) include terms that are consistent with the intellectual property provisions set
                forth in this Agreement. As soon as reasonably practicable after execution of any sublicense agreement with a Sublicensee after the Restatement Date, [***]. In addition, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zdec6bd2550864879bcc158d144acbdb3">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.3.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Responsibility for Sublicensees and Subcontractors</font>. Notwithstanding any sublicense, the sublicensing or subcontracting Party will remain primarily liable to the other Party for the performance of
                all of its obligations under, and such Party&#8217;s compliance with all provisions of, this Agreement. Each Party agrees that it will be fully responsible and liable for any breach of the terms of this Agreement by any of its Sublicensees or
                Subcontractors to the same extent as if such Party itself has committed any such breach.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z926da0b7a5c94179bbdc453d44536238">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Collaboration Technology Enabling License</font>. Subject to the terms and conditions of this Agreement (and without limiting the licenses granted to Otsuka under <u>Section 2.1</u> (License Grants to
                Otsuka)), Otsuka hereby grants Ionis a fully-paid, royalty-free, irrevocable, worldwide, non-exclusive, sublicensable (through multiple tiers) license under any Otsuka Collaboration Know-How and Otsuka Collaboration Patent Rights (excluding
                any Product-Specific Patents) to Exploit products that include an oligonucleotide as an active pharmaceutical ingredient (other than a Licensed Product); <font style="font-style: italic;">provided</font> that Ionis may only grant a
                sublicense under the rights granted in this <u>Section 2.4</u> (Collaboration Technology Enabling License) if such sublicense includes the grant of a license under Know-How or Patent Rights Controlled by Ionis or its Affiliates to Exploit
                such products that include an oligonucleotide as an active pharmaceutical ingredient (other than a Licensed Product).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">3</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3428aa5117644c749181d9eeec8e9ba9">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">No Other Rights and Retained Rights; Negative Covenant</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z975496a36b2e4e7a8dfd16ab188ce249">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.5.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">No Other Rights and Retained Rights</font>. Nothing in this Agreement will be interpreted to grant a Party any rights under any intellectual property rights owned or Controlled by the other Party,
                including Ionis Technology or Otsuka Technology, in each case, that are not expressly granted herein, whether by implication, estoppel, or otherwise. Otsuka will not practice the Ionis Technology other than as expressly licensed and
                permitted under this Agreement and Ionis will not practice the Otsuka Technology other than as expressly licensed and permitted under this Agreement. Any rights not expressly granted to a Party by the other Party under this Agreement are
                hereby retained by such other Party. Without limiting the foregoing, (a) Ionis hereby expressly retains the right to perform (i) Development activities for the Licensed Products worldwide in accordance with the Cross-Territory Clinical
                Development Plan and the Non-Clinical HAE Development Plans, (ii) Manufacturing activities worldwide, and (iii) Ionis&#8217; other obligations under this Agreement, and (b) Otsuka hereby expressly retains the right to perform Development
                activities for the Licensed Products in the Field in the Otsuka Territory in accordance with the Otsuka Territory-Specific Development Plans solely for Commercialization and for the conduct of Medical Affairs for such Licensed Products in
                the Field in the Otsuka Territory and to Manufacture the Licensed Products in the Field in the Territory solely for Commercialization and for the conduct of Medical Affairs for such Licensed Products in the Field in the Otsuka Territory, in
                each case, in accordance with this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7396410bbe054189aed5dc73c1592753">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.5.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Negative Covenant</font>. Ionis shall not, and shall cause its Affiliates to not, grant or convey any right to any Third Party (pursuant to a license grant, collaboration or services agreement, option
                grant, or otherwise) that would be in conflict with, limit the scope of, or otherwise adversely affect the licenses granted to Otsuka pursuant to <u>Section 2.1</u> (License Grants to Otsuka).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3afa196a95b74d11933cb866fc68fa35">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.6</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Existing Third-Party IP Agreements</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zef96149bb55c4983b8f33f6067376d82">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.6.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Compliance</font>. Otsuka acknowledges and agrees that (a) the rights and licenses granted to Otsuka under this Agreement are subject to the applicable terms of all Existing Third-Party IP Agreements with
                respect to the Ionis Technology that is being sublicensed thereunder to Otsuka, (b) Ionis&#8217; ability to comply with its obligations, and grant rights and licenses to Otsuka, under this Agreement are limited by any and all requirements and
                restrictions imposed on Ionis under the Existing Third-Party IP Agreements with respect to the Ionis Technology that is being sublicensed to Otsuka by Ionis under such Existing Third-Party IP Agreements, and (c) Ionis will not be required
                to take any action or inaction pursuant to this Agreement that would cause Ionis to be in breach of any Existing Third-Party IP Agreement or to grant any rights to Otsuka hereunder that are in violation of, or inconsistent with, any
                Existing Third-Party IP Agreement. Otsuka will abide by the applicable terms of the Existing Third-Party IP Agreements, and, subject to [***], the applicable terms of any amendments, in each case, to the extent such terms are disclosed in
                the copies of the Existing Third-Party IP Agreements, and amendments thereto, that are provided or made available to Otsuka.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">4</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z04fabbb3ce63448ab7f1333f6b0e4a72">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.6.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Existing Third-Party IP Amendments</font>. During the Term, Ionis will promptly furnish Otsuka with copies of any amendment to any Existing Third-Party IP Agreement to the extent related to any of the
                rights sublicensed to Otsuka hereunder, from which copies Ionis may redact confidential or commercially sensitive information or other information that is not relevant to the rights sublicensed to Otsuka pursuant to the applicable Existing
                Third-Party IP Agreement. During the Term, Ionis shall: (a) [***]; (b) [***]; (c) [***]; and (d) [***]. Notwithstanding any provision to the contrary in this Agreement, as between the Parties, [***] shall be solely responsible for the
                payment of all license fees, royalties, milestone payments, and other payment obligations under all Existing Third-Party IP Agreements.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc88d5c4ea1d54584b93f72494320c679">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.7</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">New Third-Party IP Agreements</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd0334096a2984851ba8857e12e252b8c">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.7.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Identification of New In-License Agreements</font>. If either Party intends to obtain Control of any Patent Rights or Know-How from a Third Party (whether by acquisition or license) that such Party
                believes are [***] to Exploit the Licensed Compound or a Licensed Product (other than in connection with a Change of Control of a Party or as a result of the acquisition by a Party of a Third Party by merger, acquisition, or similar
                transaction or series of related transactions) (such Patent Rights and Know-How, &#8220;<font style="font-weight: bold; font-style: italic;">Identified Rights</font>&#8221;), then such Party will notify the other Party of the Identified Rights.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3b1f77a822b34d729508b668d57e0c13">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.7.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Potential In-Licenses</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6837742d8f794bb8a1cc89cf027f96ff">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Acquisition of Potential In-Licenses</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z90b5b1e69a1b4fc1b78853da9b2f8053">

          <tr>
            <td style="width: 111.6pt;"><br>
            </td>
            <td style="width: 32.4pt; vertical-align: top;">(i)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>[***] that [***] in the Exploitation of a Licensed Product in [***] Territory, whether by license or acquisition, (each agreement to license or acquire such Identified Rights, a &#8220;<font style="font-weight: bold; font-style: italic;">Potential




                  In-License</font>&#8221;) in accordance with this <u>Section 2.7.2</u> (Potential In-Licenses). If [***] after the Restatement Date, then [***] will [***]. If [***] pursuant to this <u>Section 2.7.2(a)</u> (Acquisition of Potential
                In-Licenses), then [***] with respect to [***] to Exploit the Licensed Products. [***] such Potential In-License will [***]. [***]. If the Identified Rights to be licensed or acquired under a Potential In-License would constitute Ionis Core
                Technology or Ionis Manufacturing and Analytical Technology if such Identified Rights were Controlled by Ionis (any such Identified Rights, &#8220;<font style="font-weight: bold; font-style: italic;">Core or Manufacturing Identified Rights</font>&#8221;)




                then, [***], [***] will have the first right to enter into such Potential In-License (a &#8220;<font style="font-weight: bold; font-style: italic;">Core or Manufacturing Potential In-License</font>&#8221;) in accordance with <u>Section 2.7.2(c)(i)</u>
                ([***] Potential In-Licenses).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z33ccc8e4022145f0b435dc651d7dda1c">

          <tr>
            <td style="width: 111.6pt;"><br>
            </td>
            <td style="width: 32.4pt; vertical-align: top;">(ii)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>If either Party [***] and if the [***], then [***]. At either Party&#8217;s request if [***] in accordance with this <u>Section 2.7.2(a)(ii)</u> (Acquisition of Potential In-Licenses), the Parties will [***]. If [***], then the Potential
                In-License [***] for all purposes of this Agreement. If [***], then Ionis will [***].<font style="font-weight: bold; font-style: italic;">&#160;</font>If Ionis [***] pursuant to this <u>Section 2.7.2(a)(ii)</u> (Acquisition of Potential
                In-Licenses) and Ionis [***] in accordance with this <u>Section 2.7.2(a)(ii)</u> (Acquisition of Potential In-Licenses),<font style="font-weight: bold; font-style: italic;">&#160;</font>then [***]. If Ionis [***], then Otsuka will [***] in
                accordance with the terms of this <u>Section 2.7.2(a)(ii)</u> (Acquisition of Potential In-Licenses) and Otsuka will [***]. </div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">5</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb43fe042c5004b74842aed2cf0a99482">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Collaboration In-Licenses</font>. For any Potential In-License that [***] in accordance with <u>Section 2.7.2(a)</u> (Acquisition of Potential In-Licenses), and for [***], (i) such Potential In-License
                will [***], (ii) the Party [***] will [***], to the extent set forth in <u>Section 2.7.2(a)(ii)</u> (Acquisition of Potential In-Licenses), (iii) the Patent Rights or Know-How in-licensed under such [***], and (iv) (A) each Party will
                [***], and (B) the Parties will [***]. The Party that [***] will [***] pursuant to this <u>Section 2.7.2(b)</u> (Collaboration In-Licenses), and such other Party will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z634c28f64f7545ab84c1f4e780287621">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">[</font>***<font style="font-weight: bold;">] Potential In-Licenses</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zff9a734999974b6ebcd13657b2c51714">

          <tr>
            <td style="width: 111.6pt;"><br>
            </td>
            <td style="width: 32.4pt; vertical-align: top;">(i)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>If the [***] a Potential In-License [***], then (A) such Potential In-License [***], (B) subject to <u>Section 2.7.2(c)(ii)</u> ([***] Potential In-Licenses), the Patent Rights and Know-How in-licensed under such Potential In-License
                [***], (C) except as set forth in clause (D) of this <u>Section 2.7.2(c)(i)</u> ([***] Potential In-Licenses), Ionis will [***] and, subject to <u>Section 2.7.2(c)(ii)</u> ([***] Potential In-Licenses), will [***]; <font style="font-style: italic;">provided</font> that if such Potential In-License [***], then [***], and Ionis [***] in accordance with <u>Section 2.7.2(c)(ii)</u> ([***] Potential In-Licenses), then Otsuka [***], and (D) if such Potential
                In-License (1) was [***] pursuant to <u>Section 2.7.2(a)</u> (Acquisition of Potential In-Licenses), (2) was not [***], and (3) is not [***], then [***] in accordance with this Agreement [***], and the terms of this <u>Section 2.7.2</u>
                (Potential In-Licenses) [***].<font style="font-weight: bold; font-style: italic;">&#160;</font>If Ionis [***] in accordance with <u>Section 2.7.2(a)</u> (Acquisition of Potential In-Licenses),<font style="font-weight: bold; font-style: italic;">&#160;</font>then Otsuka [***]. If Ionis [***], then Otsuka [***] in accordance with this <u>Section 2.7.2(c)(i)</u> ([***] Potential In-Licenses) and Otsuka will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z151209839ce34427abd4d6d7e1b8b5ea">

          <tr>
            <td style="width: 111.6pt;"><br>
            </td>
            <td style="width: 32.4pt; vertical-align: top;">(ii)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>If Ionis [***],<font style="font-size: 12pt;">&#160;</font>then Ionis<font style="font-size: 12pt;"> [</font>***]. If Ionis [***] in accordance with <u>Section 2.7.2(c)(i)</u> ([***] Potential In-Licenses), then Ionis will [***]. Ionis may
                [***]. Within [***], Otsuka will [***]. If Otsuka [***] in accordance with this <u>Section 2.7.2(c)(ii)</u> ([***] Potential In-Licenses), then such [***] and <u>Section 2.7.2(b)</u> (Collaboration In-Licenses) will apply, <font style="font-style: italic;">mutatis mutandis</font>. If Otsuka [***] in accordance with this <u>Section 2.7.2(c)(ii)</u> ([***] Potential In-Licenses), then Otsuka [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z01e097c189134251a9e56efd93d487cd">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.8</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Right of First Negotiation for Follow-On Products</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z939695a00fd04a479c777248ecc9ceb0">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.8.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">ROFN Exercise</font>. If (a) during the period from the Original Effective Date until the [***] (such period, the &#8220;<font style="font-weight: bold; font-style: italic;">Europe ROFN Period</font>&#8221;), Ionis
                intends to grant rights to a Third Party that include the right to Commercialize [***] designed to bind to the RNA encoding PKK for the treatment of HAE (any such compound, a &#8220;<font style="font-weight: bold; font-style: italic;">Follow-On
                  Product</font>&#8221;) in the Europe Territory or (b) during the period from the Restatement Date until the [***] (such period, the &#8220;<font style="font-weight: bold; font-style: italic;">Asia ROFN Period</font>&#8221;; <font style="font-style: italic;">provided</font> that [***] Ionis intends to grant rights to a Third Party that include the right to Commercialize a Follow-On Product in the Asia Territory, then, in each case ((a) or (b)) Ionis will provide to Otsuka (i) notice
                of whether Ionis intends to grant Commercialization rights to such proposed Follow-On Product in the Europe Territory, Asia Territory or both (such applicable countries within the Europe Territory or the Asia Territory, the &#8220;<font style="font-weight: bold; font-style: italic;">ROFN Territory</font>&#8221;; <font style="font-style: italic;">provided</font> that the ROFN Territory will not include any countries within the Europe Territory if the Europe ROFN Period has
                expired or any countries within the Asia Territory if the Asia ROFN Period has expired) and the proposed scope of Commercialization rights that Ionis proposes to grant, and (ii) an information package containing, to the extent such
                information is in Ionis&#8217; or its Affiliate&#8217;s Control: (A) summaries of [***], (B) information about [***], (C) a summary of [***], and (D) [***] related to the Follow-On Product to the extent necessary or reasonably useful for Otsuka to
                evaluate whether to obtain rights with respect to Follow-On Product (&#8220;<font style="font-weight: bold; font-style: italic;">ROFN Notice and Package</font>&#8221;). Promptly thereafter, Ionis will provide a high-level presentation to the JSCs (at a
                joint meeting), if during the Europe ROFN Period, or to the Asia JSC, if during the Asia ROFN Period after expiration of the Europe ROFN Period, relating to the Follow-On Product and the rights Ionis proposes to grant. Otsuka will have an
                exclusive right, exercisable no later than [***] after receipt of a ROFN Notice and Package from Ionis containing all information set forth in the foregoing clauses ((A) through (D)) to the extent such information is in Ionis&#8217; or its
                Affiliate&#8217;s Control, to notify Ionis in writing as to whether Otsuka desires to negotiate for such rights to Commercialize such Follow-On Product in the applicable ROFN Territory (a &#8220;<font style="font-weight: bold; font-style: italic;">ROFN
                  Exercise Notice</font>&#8221;). During such [***], Ionis will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">6</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8bcabdd58999434297849988853dc7f9">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.8.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Negotiation</font>. If Otsuka provides a ROFN Exercise Notice to Ionis within such [***], then the Parties will negotiate in good faith for [***] from the date of Ionis&#8217; receipt of the ROFN Exercise
                Notice, or such longer period as may be agreed upon in writing by the Parties (the &#8220;<font style="font-weight: bold; font-style: italic;">ROFN Negotiation Period</font>&#8221;) the terms of a definitive agreement (or amendment to this Agreement)
                pursuant to which Ionis would grant to Otsuka the rights to Commercialize (and, as agreed by the Parties, to otherwise Exploit) such Follow-On Product in the applicable ROFN Territory. Neither Party will have any obligation to enter into
                any agreement or amendment to this Agreement granting rights to Otsuka to Commercialize or otherwise Exploit such Follow-On Product in the applicable ROFN Territory. If the ROFN Negotiation Period expires before the Parties have entered
                into an agreement or amendment to this Agreement with respect to Otsuka&#8217;s Commercialization or other Exploitation of such Follow-On Product in the applicable ROFN Territory, and if such ROFN Negotiation Period [***] in such ROFN Territory,
                then Ionis will have the right to negotiate and enter into an agreement with any Third Party with respect to a grant of rights to Exploit such Follow-On Product in such ROFN Territory [***]. If Ionis does not grant rights to a Third Party
                that include the right to Commercialize such Follow-On Product in the applicable ROFN Territory [***], then the terms of this <u>Section 2.8</u> (Right of First Negotiation for Follow-On Products) will [***]. If the [***] in such ROFN
                Territory expires before the Parties have entered into an agreement or amendment to this Agreement with respect to Otsuka&#8217;s Commercialization or other Exploitation of such Follow-On Product in such ROFN Territory then Ionis will have no
                further obligation to negotiate with Otsuka with respect to any grant of such rights to Otsuka and will be free to negotiate and enter into an agreement with any Third Party with respect to a grant of rights to Exploit such Follow-On
                Product in such ROFN Territory.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z99f862d824474e8f9256a8e57b7424df">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">2.8.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Follow-On Product Activities</font>. If Ionis enters into an agreement with a Third Party granting any rights to Exploit a Follow-On Product, then all Development, Commercialization, and Medical Affairs
                activities related to such Follow-On Product (&#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Product Activities</font>&#8221;)<font style="font-weight: bold; font-style: italic;">&#160;</font>will be subject to the following: (a)
                [***] related to such Follow-On Product; and (b) Ionis and its Affiliates shall conduct the Follow-On Product Activities independently of the activities under this Agreement and [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">7</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; font-weight: bold;">ARTICLE 3</div>
      <div style="text-align: center; font-weight: bold;">TECHNOLOGY TRANSFER</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1e4d154e8b8c487b9bc7d0feb53daff4">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">3.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Initial Know-How Transfer</font>. At a time period to be agreed upon by the Parties after the Restatement Date, Ionis will provide and transfer, and in any event will initiate such transfer within [***]
                after the Restatement Date, to Otsuka copies of the Ionis Know-How (other than Ionis Manufacturing and Analytical Know-How, the transfer of which will be conducted pursuant to <u>Section 7.4</u> (Manufacturing Technology Transfer)) that
                (a) exists on the Restatement Date, (b) was not previously provided to Otsuka, and (c) is [***] to Develop, Commercialize or conduct Packaging and Labeling or Medical Affairs for a Licensed Product (such transfer, the &#8220;<font style="font-weight: bold; font-style: italic;">Initial Know-How Transfer</font>&#8221;). Ionis may make such Ionis Know-How available in such reasonable form as maintained by Ionis. In addition to the Initial Know-How Transfer, upon Otsuka&#8217;s
                reasonable request during the Term, Ionis will provide and transfer to Otsuka copies of or otherwise make available to Otsuka all Ionis Know-How (other than Ionis Manufacturing and Analytical Know-How) not previously provided to Otsuka
                hereunder to the extent such Ionis Know-How is [***] to Develop, Commercialize or conduct Packaging and Labeling or Medical Affairs for a Licensed Product, including in accordance with <u>Section 4.7</u> (Data Transfer), <u>Section 5.6</u>
                (Cooperation), <u>Section 6.1.2</u> (Commercialization in the Otsuka Territory), <u>Section 6.2</u> (Commercialization and Medical Affairs Reporting), and <u>Section 7.1.1</u> (Ionis Manufacturing) (the &#8220;<font style="font-weight: bold; font-style: italic;">Continuing Know-How Transfer</font>,&#8221; and together with the Initial Know-How Transfer, the &#8220;<font style="font-weight: bold; font-style: italic;">Technology Transfer</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3100a64dcde8406487a25bb5e9351c1a">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">3.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Technology Transfer Costs</font>. Ionis will conduct the Technology Transfer, and will provide consultation and assistance with [***] to provide support set forth in <u>Section 7.1.1</u> (Ionis
                Manufacturing) (any such consultation, assistance, or support provided by [***]. Ionis will [***] in connection with the Initial Know-How Transfer, including, for clarity, [***]. In addition, Ionis will [***] in providing Requested
                Assistance to Otsuka in connection with such Continuing Know-How Transfer; <font style="font-style: italic;">provided</font> that, with respect to Requested Assistance related to [***] until [***] and, thereafter, [***]. After [***]. At
                all times, (a) Otsuka will [***]. Ionis may [***] following [***]. Ionis shall [***]. Notwithstanding the foregoing, [***]. For clarity, the terms of this <u>Section 3.2</u> (Technology Transfer Costs) shall not apply with respect to [***]
                and, for clarity, the terms of this <u>Section 3.2</u> (Technology Transfer Costs) shall not apply to [***]. Notwithstanding any provision to the contrary, Ionis&#8217; obligations to conduct the Technology Transfer and provide Requested
                Assistance will not require Ionis to conduct any additional Clinical Trials or generate any additional data or information that is not expressly contemplated by the Cross-Territory Clinical Development Plan or the Non-Clinical HAE
                Development Plans. Notwithstanding any provision to the contrary in this <u>Section 3.2</u> (Technology Transfer Costs), if Ionis provides to Otsuka any Requested Assistance or Continuing Know-How Transfer, in each case, related to the
                Europe Territory, then to the extent such Requested Assistance or Continuing Know-How Transfer is applicable to the Asia Territory and to the extent feasible, Otsuka will seek such support or assistance from Otsuka&#8217;s Affiliates rather than
                requesting additional Requested Assistance or a Continuing Know-How Transfer from Ionis.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">ARTICLE 4</div>
      <div style="text-align: center; font-weight: bold;">DEVELOPMENT</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zec423d0713b9493cb34ef1b947b6e26a">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Development Diligence Obligations</font>. Ionis will be responsible for conducting the activities under the Cross-Territory Clinical Development Plan (other than with respect to Clinical Trial sites in
                Japan, if applicable) and both of the Non-Clinical HAE Development Plans (other than with respect to any activities allocated to Otsuka under the Non-Clinical Asia HAE Development Plan) and will use Commercially Reasonable Efforts to carry
                out such activities. For clarity, Ionis shall not conduct any [***]. Otsuka will be responsible for conducting the activities under the Europe Territory-Specific Development Plan, the Asia Territory-Specific Development Plan, and solely to
                the extent any activities are allocated to Otsuka under the Non-Clinical Asia HAE Development Plan, the Non-Clinical Asia HAE Development Plan, [***]. Notwithstanding the foregoing, if, as provided in <u>Section 4.4.1(c)(ii)</u> (Shared
                Development Costs), the Parties agree to update the Cross-Territory Clinical Development Plan (including the Shared Development Budget) to include [***], then Otsuka will [***]. Each Party will conduct all Development activities for which
                it is responsible under this Agreement in a good scientific manner, in accordance with GLP and GCP, as applicable, and in compliance with Professional Requirements and Applicable Law.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">8</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z65f6fa4964ec4ee6b39e2d54f330ad95">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">&#160;Development Plans</font><font style="color: rgb(0, 0, 0);">.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd6ea8a7339ed47099473750c83c6f8e0">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">4.2.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Cross-Territory Clinical Development Plan</font>. The current development plan for the clinical Development activities for both the Europe Territory and the Ionis Territory is set forth on <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 4.2.1</u> (such development plan as it may be modified in accordance with the terms and conditions of this Agreement, the &#8220;<font style="font-weight: bold; font-style: italic;">Cross-Territory




                  Clinical Development Plan</font>&#8221;). The current Cross-Territory Clinical Development Plan includes (and any updates to the Cross-Territory Clinical Development Plan will at all times include) all Clinical Trials that are intended to
                support obtaining or maintaining Regulatory Approval for any Licensed Product in both the Europe Territory and the Ionis Territory (and Japan, if the Parties agree to include Clinical Trial sites in Japan for any Cross-Territory Clinical
                Study as provided in <u>Section 4.4.1(c)(ii)</u> (Shared Development Costs)) (any such Clinical Trials, &#8220;<font style="font-weight: bold; font-style: italic;">Cross-Territory Clinical Studies</font>&#8221;), including (a) all Cross-Territory
                Clinical Studies that were ongoing as of the Original Effective Date (the &#8220;<font style="font-weight: bold; font-style: italic;">Ongoing Cross-Territory Studies</font>&#8221;), (b) all Post-Approval Mandatory Studies that are (i) required to
                support maintaining Regulatory Approval for any Licensed Product in both the Europe Territory and the Ionis Territory and (ii) designed to meet the requirements of the EMA for maintaining Regulatory Approval of the Licensed Product in the
                Europe Territory (collectively ((i) and (ii)), &#8220;<font style="font-weight: bold; font-style: italic;">Post-Approval Cross-Territory Mandatory Studies</font>&#8221;), and (c) all future Cross-Territory Clinical Studies for [***]. From time to time
                during the Term, either Party may submit to the Europe JSC any proposed update to the Cross-Territory Clinical Development Plan to include additional Cross-Territory Clinical Studies, including the study designs for such additional
                Cross-Territory Clinical Studies. In addition, each Party shall submit to the Europe JSC (or other designated Subcommittee) reasonably in advance proposed updates to the Cross-Territory Clinical Development Plan to take into account changed
                circumstances, such as cessation of any Cross-Territory Clinical Study, or the need to amend any Cross-Territory Clinical Study, including amendments in response to Regulatory Authority requirements, for safety reasons or otherwise. The
                Europe JSC will review, discuss, and determine whether to approve each update to the Cross-Territory Clinical Development Plan. Once reviewed and approved by the Europe JSC (or the Executive Committee, if the Europe JSC cannot agree), each
                update to the Cross-Territory Clinical Development Plan will automatically become effective and supersede the previous Cross-Territory Clinical Development Plan, as of the date of such approval by the Europe JSC (or Executive Committee).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5b4cd232f3774e6db613abea06b73f0d">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">4.2.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Non-Clinical HAE Development Plans</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z84d39fbfaa404649be01bf7f596b532b">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Europe Territory</font>. The current development plan for all CMC Development and non-clinical Development, in each case, required to obtain and maintain Regulatory Approval for the Licensed Product for
                the treatment of HAE in the Europe Territory is set forth on <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 4.2.2</u> (such development plan, as it may be modified in accordance with the terms and conditions of this
                Agreement, the &#8220;<font style="font-weight: bold; font-style: italic;">Non-Clinical Europe HAE Development Plan</font>&#8221;). From time to time during the Term, either Party may submit to the Europe JSC any proposed update to the Non-Clinical
                Europe HAE Development Plan to include additional CMC Development or non-clinical Development activities required to obtain or maintain Regulatory Approval for the Licensed Product for the treatment of HAE in the Europe Territory. In
                addition, each Party shall submit to the Europe JSC reasonably in advance proposed updates to take into account changed circumstances or the need to amend any CMC Development or non-clinical Development activities for the Licensed Product
                for the treatment of HAE in the Europe Territory. The Europe JSC will review, discuss, and determine whether to approve each update to the Non-Clinical Europe HAE Development Plan. Once reviewed and approved by the Europe JSC (or the
                Executive Committee, if the Europe JSC cannot agree), each update to the Non-Clinical Europe HAE Development Plan will automatically become effective and supersede the previous Non-Clinical Europe HAE Development Plan as of the date of such
                approval by the Europe JSC (or Executive Committee).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">9</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf734ac0a46644d70b99c86c97a4095f5">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Asia Territory</font>. If any CMC Development or non-clinical Development is required by a Regulatory Authority in the Asia Territory to obtain and maintain Regulatory Approval for the Licensed Product
                for the treatment of HAE in the Asia Territory and such Development activities are not set forth in the Non-Clinical Europe HAE Development Plan (such activities, &#8220;<font style="font-weight: bold; font-style: italic;">Asia-Specific
                  Non-Clinical HAE Development Activities</font>&#8221;), then Otsuka may prepare and submit to the Asia JSC a written plan pursuant to which such Asia-Specific Non-Clinical HAE Development Activities will be conducted (such development plan, as
                it may be updated in accordance with the terms and conditions of this Agreement, the &#8220;<font style="font-weight: bold; font-style: italic;">Non-Clinical Asia HAE Development Plan</font>&#8221;). The Asia JSC will review, discuss, and determine
                whether to approve the Non-Clinical Asia HAE Development Plan. From time to time during the Term, either Party may submit to the Asia JSC any proposed update to the Non-Clinical Asia HAE Development Plan to include additional Asia-Specific
                Non-Clinical HAE Development Activities and the Asia JSC will review, discuss, and determine whether to approve such update to the Non-Clinical Asia HAE Development Plan. Once reviewed and approved by the Asia JSC (or the Executive
                Committee, if the Asia JSC cannot agree), the initial Non-Clinical Asia HAE Development Plan and each update thereto will automatically become effective and supersede the previous Non-Clinical Asia HAE Development Plan as of the date of
                such approval by the Asia JSC (or Executive Committee).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z81fbcf32663748d0bc65b15620167f85">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Territory-Specific Development Plans</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z539ef9f807e44628adb5da747de79cff">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">4.3.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Europe Territory-Specific Development Plan</font>. Unless otherwise mutually agreed by the Parties, within [***], then Otsuka will prepare and submit to the Europe JSC a plan setting forth all Development
                activities that are intended to support obtaining or maintaining Regulatory Approval for the Licensed Products solely in the Europe Territory other than the activities set forth in the Non-Clinical Europe HAE Development Plan (the &#8220;<font style="font-weight: bold; font-style: italic;">Europe Territory-Specific Development Plan</font>&#8221;). If such plan is submitted by Otsuka, then the Europe JSC will review, discuss, and determine whether to approve the Europe
                Territory-Specific Development Plan. Notwithstanding the foregoing or anything to the contrary in this Agreement, the Europe Territory-Specific Development Plan (if submitted by Otsuka) will at all times include Development activities that
                are (i) necessary to obtain and maintain Regulatory Approval for at least one Licensed Product in [***] consistent with Otsuka&#8217;s obligations under <u>Section 4.1</u> (Development Diligence Obligations) and (ii) not included in the
                Cross-Territory Clinical Development Plan or the Non-Clinical Europe HAE Development Plan. For clarity, if no Development activities are necessary to obtain or maintain Regulatory Approval for at least one Licensed Product in [***], other
                than the Development activities set forth in the Cross-Territory Clinical Development Plan or the Non-Clinical Europe HAE Development Plan, then Otsuka shall not be obligated to prepare or submit to the Europe JSC a Europe
                Territory-Specific Development Plan for the HAE indication.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">10</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd6492c12a2f44547bf53ce13021827d8">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">4.3.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Asia Territory-Specific Development Plan</font>. Within [***] following the Restatement Date, Otsuka will prepare and submit to the Asia JSC a plan setting forth all Development activities that are
                intended to support obtaining or maintaining Regulatory Approval for the Licensed Products solely in the Major Asian Countries, other than the activities set forth in the Non-Clinical Europe HAE Development Plan or, if applicable, the
                activities set forth in the Non-Clinical Asia HAE Development Plan (the &#8220;<font style="font-weight: bold; font-style: italic;">Asia Territory-Specific Development Plan</font>,&#8221; and together with the Europe Territory-Specific Development Plan
                (if prepared by Otsuka), the &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory-Specific Development Plans</font>&#8221;). The Asia JSC will review, discuss, and determine whether to approve the Asia Territory-Specific
                Development Plan. Notwithstanding the foregoing or anything to the contrary in this Agreement, the Asia Territory-Specific Development Plan will at all times include Development activities that are (a) necessary to obtain and maintain
                Regulatory Approval [***] consistent with Otsuka&#8217;s obligations under <u>Section 4.1</u> (Development Diligence Obligations) and (b) not included in the Cross-Territory Clinical Development Plan or the Non-Clinical HAE Development Plans.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfe80624c16064ad9b3e811b30df18665">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">4.3.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Consistency with Cross-Territory Clinical Development Plan</font>. The Europe Territory-Specific Development Plan and the Asia Territory-Specific Development Plan will each, at all times during the Term,
                be consistent with the then-current Cross-Territory Clinical Development Plan, except to the extent such inconsistency is (a) necessary to conform with any written requirement from any Regulatory Authority or with any Applicable Law
                (including compliance requirements) in the Europe Territory or the Asia Territory, as applicable, or (b) approved by the applicable JSC (or the Executive Committee, if the applicable JSC cannot agree) (in each case by unanimous Party Vote).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z891176883b314b178c64cef39fd2c5e8">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">4.3.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Updates</font>. At least [***] during the Term (and more frequently as may be necessary), Otsuka will prepare an update to the Asia Territory-Specific Development Plan and, if applicable, the Europe
                Territory-Specific Development Plan, to amend or include additional Development activities to be conducted during the [***] Calendar Year that are intended to support obtaining or maintaining Regulatory Approval for the Licensed Products
                solely in the Europe Territory or Asia Territory, as applicable, other than the activities set forth in the Non-Clinical HAE Development Plans (or otherwise update the Development activities under the applicable Otsuka Territory-Specific
                Development Plan). The applicable JSC will review, discuss, and determine whether to approve each update to the Europe Territory-Specific Development Plan or the Asia Territory-Specific Development Plan. Once approved by the applicable JSC
                (or the Executive Committee, if the applicable JSC cannot agree), the Europe Territory-Specific Development Plan and each update thereto or the Asia Territory-Specific Development Plan and each update thereto will automatically become
                effective and, in the case of an update, supersede the previous Europe Territory-Specific Development Plan or Asia Territory-Specific Development Plan, as applicable, as of the date of such approval.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">11</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zaf5bea4d044340069baa7f9588d4cfa6">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Development Costs</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z960457accfe84b12bf73e34a799ccc8a">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">4.4.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Overview</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd26016326e1d44beb3abb9d471d5ea6e">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ionis Costs</font>. Ionis will be [***] responsible for all costs and expenses incurred in connection with the performance of the [***]. In addition, Ionis will be [***] responsible for all costs and
                expenses incurred in connection with the performance of all activities under the [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc78a2623c3f84fc3b3d179f322489494">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Costs</font>. Otsuka will be [***] responsible for all costs and expenses incurred in connection with the performance of all activities under the [***]. In addition, Otsuka will reimburse Ionis for
                [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z2f7eb26fc0e84e858c7df289d2cffbdc">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Shared Development Costs</font><font style="font-style: italic;">.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z2c9d93ba771343acbf56437f4fa3cba0">

          <tr>
            <td style="width: 111.6pt;"><br>
            </td>
            <td style="width: 32.4pt; vertical-align: top;">(i)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Subject to <u>Section 4.4.1(c)(ii)</u> (Shared Development Costs), with respect to (A) all Post-Approval Cross-Territory Mandatory Studies for the treatment of HAE that are included in the Cross-Territory Clinical Development Plan as of
                the Original Effective Date and (B) any other Post-Approval Cross-Territory Mandatory Studies for the treatment of HAE or any Future Cross-Territory Studies, in each case ((A) and (B)), that are added to the Cross-Territory Clinical
                Development Plan in accordance with <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan), the Parties will share, [***], in each case, in accordance with the Cross-Territory Clinical Development Plan and Shared Development
                Budget (such costs, &#8220;<font style="font-weight: bold; font-style: italic;">Shared Cross-Territory Development Costs</font>&#8221;) in accordance with the terms of <u>Section 4.4.3</u> (Shared Cross-Territory Development Costs).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfe0d0a673a8a484b8e6fc54e8666aa48">

          <tr>
            <td style="width: 111.6pt;"><br>
            </td>
            <td style="width: 32.4pt; vertical-align: top;">(ii)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>If (A) the Parties agree to update the Cross-Territory Clinical Development Plan (including the Shared Development Budget) to include Clinical Trial sites in Japan for any Cross-Territory Clinical Study and (B) the PMDA agrees in advance
                that such Cross-Territory Clinical Study (including the Clinical Trial sites in Japan) will be sufficient to obtain Regulatory Approval in Japan for use of the Licensed Product without the need for additional Japan-only Clinical Trials,
                then [***]; <font style="font-style: italic;">provided</font> that, if a Cross-Territory Clinical Study has been initiated as of or after the Original Effective Date and is subsequently amended to include Clinical Trial sites in Japan,
                then at the time the Parties agree to include Clinical Trial sites in Japan in such Cross-Territory Clinical Study, Ionis will provide to Otsuka a written report of the [***] (the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis
                  Incurred Development Costs</font>&#8221;). Such written report shall include [***]. Ionis will provide an invoice to Otsuka for [***] of the Ionis Incurred Development Costs, and Otsuka will pay such amount [***] after receipt of such invoice
                [***]; <font style="font-style: italic;">provided</font> that, if Otsuka disputes any invoiced amount, then Otsuka will pay the undisputed invoiced amount [***] and will pay any disputed amounts [***] following resolution of the dispute
                and determination that such amounts are owed; and <font style="font-style: italic;">provided, further</font> that Otsuka shall have the right to [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">12</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
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      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z81bbde12d7cc4b649a676b555c981d0c">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">4.4.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Shared Development Budget; Cost Overruns</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z623376bc8d8744ddacc22734e615e2d7">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Shared Development Budget</font>. The current budget for the Shared Cross-Territory Development Costs (such budget as it may be modified in accordance with the terms and conditions of this Agreement, the
                &#8220;<font style="font-weight: bold; font-style: italic;">Shared Development Budget</font>&#8221;) for the Post-Approval Cross-Territory Mandatory Studies that are included in the Cross-Territory Clinical Development Plan as of the Restatement Date
                is set forth in <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 4.4.2</u> (Shared Development Budget). With respect to each other Post-Approval Cross-Territory Mandatory Study for the treatment of HAE and each Future
                Cross-Territory Study that is subject to cost sharing by the Parties in accordance with <u>Section 4.4.1(c)</u> (Shared Development Costs), including any Cross-Territory Clinical Study that the Parties agree will include Clinical Trial
                sites in Japan, the Europe JSC (or the Executive Committee if the Europe JSC cannot agree) will develop, discuss, and determine whether to approve an update to the Shared Development Budget at the time the Europe JSC (or Executive
                Committee) reviews, discusses, and determines whether to approve the update to the Cross-Territory Clinical Development Plan applicable to such additional Cross-Territory Clinical Study. Any update to the Shared Development Budget will at
                all times include a detailed written budget for the performance of all Future Cross-Territory Studies and any additional Post-Approval Cross-Territory Mandatory Studies for the treatment of HAE, in each case, that are included in the
                Cross-Territory Clinical Development Plan (as updated). From time to time during the Term, either Party may submit to the Europe JSC any proposed update to the Shared Development Budget, including in connection with any update to the
                Cross-Territory Clinical Development Plan or to address a potential Cost Overrun. The Europe JSC will review, discuss, and determine whether to approve each update to the Shared Development Budget. Once reviewed and approved by the Europe
                JSC (or the Executive Committee if the Europe JSC cannot agree), each update to the Shared Development Budget will automatically become effective and supersede the previous Shared Development Budget, as of the date of such approval by the
                Europe JSC (or Executive Committee).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z753a914d7e8b4f7abfe6f9355841e702">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Cost Overruns</font>. Ionis (and Otsuka, if the Parties agree to include Clinical Trial sites in Japan in any Cross-Territory Clinical Study as provided in Section 4.4.1(c)(ii) (Shared Development Costs))
                [***] for a given Calendar Year [***] for such Calendar Year. Ionis (and Otsuka, if applicable) will notify the Europe JSC (or any other designated Subcommittee) without undue delay if it reasonably anticipates that the Shared
                Cross-Territory Development Costs incurred by the applicable Party are reasonably likely to exceed the applicable budgeted amounts under the then-current Shared Development Budget by more than [***] (a &#8220;<font style="font-weight: bold;">Cost
                  Overrun</font>&#8221;). Ionis (and Otsuka, if applicable) will include [***] and, to the extent reasonably possible, will [***]. Thereafter, the Europe JSC (or other designated Subcommittee) shall promptly hold an ad-hoc meeting to evaluate
                whether there are mitigation measures to prevent the Cost Overrun, and if not, the Europe JSC (or other designated Subcommittee) will discuss what steps to take to address such Cost Overrun, including updating the Shared Development Budget
                or the Cross-Territory Clinical Development Plan, as applicable. If the Europe JSC (or the Executive Committee if the Europe JSC cannot agree) does not approve an update to the Shared Development Budget to reflect the anticipated Cost
                Overrun, then [***] and, to the extent [***]. For clarity, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">13</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
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      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z31f37d464e6f430c8436692d9b0bd484">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">4.4.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Shared Cross-Territory Development Costs</font>. The Parties will share, at the [***], all Shared Cross-Territory Development Costs incurred by or on behalf of Ionis or its Affiliates and by or on behalf
                of Otsuka or its Affiliates (if the Parties agree to include Clinical Trial sites in Japan in any Cross-Territory Clinical Study as provided in <u>Section 4.4.1(c)(ii)</u> (Shared Development Costs)), in accordance with the Cross-Territory
                Clinical Development Plan and the amount budgeted therefor in the Shared Development Budget,<font style="font-style: italic;"> plus</font> [***] (&#8220;<font style="font-weight: bold; font-style: italic;">Eligible Cross-Territory Development
                  Costs</font>&#8221;). No later than [***] after the end of each Calendar Quarter, Ionis will deliver to Otsuka a written report specifying in reasonable detail the Eligible Cross-Territory Development Costs incurred by or on behalf of Ionis
                during such Calendar Quarter, together with reasonable supporting documentation, and if Clinical Trial sites in Japan are included in any Cross-Territory Clinical Study, Otsuka will deliver to Ionis a written report specifying in reasonable
                detail the Eligible Cross-Territory Development Costs incurred by or on behalf of Otsuka or its Affiliates during such Calendar Quarter, together with reasonable supporting documentation. Promptly thereafter, Ionis will submit to Otsuka an
                invoice (and, if there has been any change to a Payment Form previously submitted, or if a previously submitted Payment Form has expired, an updated Payment Form) for Otsuka&#8217;s unpaid share (at the [***]) of such Eligible Cross-Territory
                Development Costs (i.e., [***]) or, if applicable, Ionis will submit to Otsuka a statement of Ionis&#8217; unpaid share (at the [***]) of such Eligible Cross-Territory Development Costs. No later than [***] after Otsuka&#8217;s receipt of such invoice
                (and updated Payment Form, if applicable) for such Calendar Quarter, Otsuka will make a balancing payment to Ionis equal to Otsuka&#8217;s unpaid share of the total Eligible Cross-Territory Development Costs to effect the [***] for such Eligible
                Cross-Territory Development Costs (or, if applicable, no later than [***] after Ionis&#8217; submission of a statement to Otsuka, Ionis will make a balancing payment to Otsuka equal to Ionis&#8217; unpaid share of the total Eligible Cross-Territory
                Development Costs to effect the [***] for such Eligible Cross-Territory Development Costs); <font style="font-style: italic;">provided</font> that, if Otsuka disputes any invoiced amount, then Otsuka will pay the undisputed invoiced amount
                within such [***] and will pay any disputed amounts within [***] following resolution of the dispute and determination that such amounts are owed.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zabd1018702d04befa91e90a61251dc2c">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">4.4.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Future Cross-Territory Studies for [</font>***<font style="font-weight: bold;">]</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z97ee3ed4c26648c297568f26dc3cf777">

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            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Shared Costs</font>. At any time during the Term, either Party may propose that the Parties clinically Develop a Licensed Product [***]. Such Party will submit a proposal to the Europe JSC setting forth
                the proposed clinical Development activities in the Europe Territory, Japan, or the Ionis Territory for such [***] and a timeline and budget for such activities (a [***]). The Europe JSC (or the Executive Committee if the Europe JSC cannot
                agree) will review, discuss, and determine whether to approve such [***], either as proposed or as may be revised by agreement of the Europe JSC (or Executive Committee), within [***] of the submission thereof. If the Europe JSC (or
                Executive Committee) approves such [***], as proposed or as revised per the agreement of the Parties, then (i) the Europe JSC (or Executive Committee) will approve an update to the Cross-Territory Clinical Development Plan in accordance
                with <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan) and to the Shared Development Budget in accordance with <u>Section 4.4.2(a)</u> (Shared Development Budget) to include any Future Cross-Territory Studies in the Europe
                Territory, Japan, or the Ionis Territory (as applicable) for such [***] and (ii) the Parties will share the cost of any Eligible Cross-Territory Development Costs incurred in connection with the performance of such Future Cross-Territory
                Studies in accordance with <u>Section 4.4.3</u> (Shared Cross-Territory Development Costs).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">14</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf10a8c408939430d8353c029019493a2">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">[</font>***<font style="font-weight: bold;">] by Ionis</font>. If the Europe JSC (or the Executive Committee if the Europe JSC cannot agree) does not approve a [***] for a given [***] or does not approve
                an updated Cross-Territory Clinical Development Plan in accordance with <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan) or Shared Development Budget in accordance with <u>Section 4.4.2(a)</u> (Shared Development Budget)
                to include the Future Cross-Territory Studies for such [***], then (i) Ionis will have the right, but not the obligation, to proceed with the Development of such [***] in the Territory as contemplated by such [***] with such modifications
                as Ionis deems appropriate [***] (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis [</font>***<font style="font-weight: bold; font-style: italic;">]</font>&#8221;) and such Development will be conducted outside the Cross-Territory
                Clinical Development Plan; and (ii) notwithstanding the licenses, rights of reference, and other rights granted to Otsuka under this Agreement, Otsuka will not have any license or rights to use any Ionis [***] (including any right of
                reference to use such Ionis [***] contained in the related Regulatory Submissions by Ionis and notwithstanding the inclusion of any such data in the Ionis Technology) in support of any Regulatory Submissions or Regulatory Approval for the
                Licensed Product in the Europe Territory or in the Commercialization of such Licensed Product in the Europe Territory, unless and until [***], <font style="font-style: italic;">provided</font> that Otsuka may use safety data in connection
                with such Ionis [***] solely to satisfy any safety-related reporting obligations to Regulatory Authorities related to Licensed Products in the Europe Territory without [***]. For clarity, Ionis [***]. For further clarity, the terms of
                clause (ii) in this <u>Section 4.4.4(b)</u> ([***] by Ionis) do not apply with respect to [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3ca8e4c432754f79b99538ae60a7c8c1">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Opt-In</font>. If Ionis conducts any Ionis [***] pursuant to <u>Section 4.4.4(b)</u> ([***] by Ionis), then Ionis shall provide Development reports to Otsuka related to such Ionis [***] in
                accordance with <u>Section 4.5</u> (Development Reports), and Otsuka shall have the right, [***] to opt-in with respect to such Ionis [***] in accordance with this <u>Section 4.4.4(c)</u> (Otsuka Opt-In). Upon Otsuka&#8217;s written request,
                Ionis shall provide to Otsuka a written report of the Internal Costs and External Costs, in each case, incurred directly by or on behalf of Ionis or its Affiliates as of the date of such written request in the performance of such Ionis
                [***] (the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis [</font>***<font style="font-weight: bold; font-style: italic;">] Costs</font>&#8221;). Such written report shall include supporting documentation of the External Costs
                included within the Ionis [***] Costs. Otsuka shall have the right, exercisable during the [***] period after receipt of such report, to provide notice to Ionis that Otsuka wishes to share the costs of such Ionis [***] (&#8220;<font style="font-weight: bold; font-style: italic;">Opt-In Notice</font>&#8221;). Following the receipt of an Opt-In Notice, Ionis shall provide an invoice to Otsuka for [***] of such Ionis [***] (&#8220;<font style="font-weight: bold; font-style: italic;">Opt-In Fee</font>&#8221;) as follows: [***]. Otsuka shall pay the Opt-In Fee within [***] after receipt of such invoice and supporting documentation; <font style="font-style: italic;">provided</font> that, if Otsuka disputes any
                invoiced amount, then Otsuka will pay the undisputed invoiced amount within such [***] and will pay any disputed amounts within [***] following resolution of the dispute and determination that such amounts are owed. Following Otsuka&#8217;s
                payment of the Opt-In Fee, (A) the Ionis [***] shall be deemed a Future Cross-Territory Study and will be added to the Cross-Territory Clinical Development Plan, (B) the Parties will share [***] all Internal Costs reasonably incurred and
                External Costs incurred, in each case, directly by or on behalf of Ionis or its Affiliates in the performance of the Ionis [***] from the date on which Ionis provides a written report of the Ionis [***] Costs, (C) the applicable Ionis [***]
                shall be included within Ionis Know-How and subject to the licenses in <u>Section 2.1</u> (License Grants to Otsuka), and (D) the Ionis [***] included in related Regulatory Submissions will be subject to Otsuka&#8217;s right of use and right of
                reference provided in <u>Section 5.9</u> (Right of Reference).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">15</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z520fd5e7d02443f2a3902ffbb3def715">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(d)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Use in the Asia Territory</font>. For clarity, if Ionis Develops the Licensed Product in a [***] in accordance with <u>Section 4.4.4(b)</u> ([***] by Ionis), then (i) Otsuka will have the right,
                at Otsuka&#8217;s [***], to Develop, seek Regulatory Approval for, and otherwise Exploit the Licensed Product in such [***] in the Asia Territory in accordance with this Agreement, (ii) the applicable Ionis [***] shall be included within Ionis
                Know-How and subject to the licenses in <u>Section 2.1</u> (License Grants to Otsuka) solely to the extent such licenses relate to the Asia Territory, and (iii) the Ionis [***] included in related Regulatory Submissions will be subject to
                Otsuka&#8217;s right of use and right of reference provided in <u>Section 5.9</u> (Right of Reference) solely in the Asia Territory, in each case, regardless of whether Otsuka has opted in to Ionis [***] in accordance with <u>Section 4.4.4(c)</u>
                (Otsuka Opt-In). For further clarity, if the Parties agree (through the Europe JSC or the Executive Committee) on a [***] that includes Clinical Trial sites in Japan, the last sentence of <u>Section 4.4.4(a)</u> (Shared Costs) shall apply
                and Otsuka will share the applicable Eligible Cross-Territory Development Costs in accordance with <u>Section 4.4.3</u> (Shared Cross-Territory Development Costs).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z35db97154d20404a83df896140e85cd9">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Development Reports</font>. At each meeting of the Europe JSC or Asia JSC, as applicable, Ionis and Otsuka will each provide (a) the Europe JSC with (i) a written summary of the activities conducted by or
                on behalf of such Party under the Cross-Territory Clinical Development Plan, and with respect to Ionis, [***], in each case ((a) and (b)), since the last Europe JSC meeting or Asia JSC meeting, as applicable, including patient enrollment,
                the ongoing status, and material results of all Clinical Trials for the Licensed Products conducted by or on behalf of such Party. Each Party will also promptly provide written notice to the other Party and keep the other Party reasonably
                informed, (A) through the Europe JSC or Alliance Managers, of (i) any significant Development events under the Cross-Territory Clinical Development Plan, and with respect to Ionis, any additional Development activities conducted by or on
                behalf of Ionis or any of its Affiliates for the Licensed Product that are not set forth in the Cross-Territory Clinical Development Plan or the Non-Clinical HAE Development Plans, and (ii) any significant Development events under the
                Non-Clinical Europe HAE Development Plan or the Europe Territory-Specific Development Plan and (B) through the Asia JSC or Alliance Managers, of any significant Development events under&#160;the Non-Clinical Asia HAE Development Plan and Asia
                Territory-Specific Development Plan, in each case ((A) and (B)), that [***] the Development activities of the other Party under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z250e16d073ef405981b4a5923aa02b74">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.6</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Development Records; Cooperation</font>. Each Party and its Affiliates will maintain written or electronic records, in sufficient detail, in a good scientific manner, in accordance with Applicable Law
                (including GLP, GCP, and GMP, as applicable), and appropriate for regulatory and patent purposes, and that are complete and accurate and reflect all Development work performed and results achieved, in each case, by or on behalf of such
                Party and its Affiliates under, as applicable, the Cross-Territory Clinical Development Plan, the Non-Clinical HAE Development Plans, and the Otsuka Territory-Specific Development Plans, and with respect to Ionis, [***]. Each Party shall
                retain such records for at least three years after the end of the Term or for such longer period as may be required by Applicable Law. The Parties will cooperate with each other to achieve the Development objectives contemplated herein in a
                timely, accurate, and responsive manner. Without limiting the foregoing, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">16</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd85ea2b3302645aa83c8a42163d2b7fd">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.7</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Data Transfer</font>. Upon Otsuka&#8217;s reasonable request, Ionis shall provide to Otsuka, [***] notwithstanding the terms of <u>Section 3.2</u> (Technology Transfer Costs), true and complete copies of all
                written, graphic or electronic embodiments of non-clinical data and clinical data generated by or on behalf of Ionis or any of its Affiliates in connection with the Development of Licensed Products, including all draft and final protocols
                and final study reports and raw data, in each case, to the extent such data is (a) Controlled by Ionis or its Affiliates and (b) [***] to Exploit a Licensed Product. In addition, and without limiting the foregoing, promptly following the
                Restatement Date, Ionis shall provide to Otsuka, [***] notwithstanding the terms of <u>Section 3.2</u> (Technology Transfer Costs), electronic datasets from all Clinical Trials of the Licensed Products, in either the Clinical Data
                Interchange Standards Consortium (CDISC) standards format or in legacy format (as requested by Otsuka), together with related documents, for use in obtaining Regulatory Approvals of the Licensed Products in the Asia Territory. [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">ARTICLE 5</div>
      <div style="text-align: center; font-weight: bold;">REGULATORY AFFAIRS</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf73cf20330f549eba8355d4b4e4fe830">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Regulatory Responsible Party</font>. Ionis will be the Regulatory Responsible Party for the Licensed Products in the Ionis Territory. Otsuka will be the Regulatory Responsible Party for the Licensed
                Products in the Otsuka Territory, <font style="font-style: italic;">provided </font>that, Ionis shall have the right to conduct regulatory activities in the Otsuka Territory, including interacting with Regulatory Authorities, solely with
                respect to (a) the Development activities for the Licensed Products in the Europe Territory for which Ionis is responsible under the Cross-Territory Clinical Development Plan and the Development activities in the Europe Territory and, if
                applicable, the Asia Territory under the Non-Clinical HAE Development Plans and (b) the Manufacturing activities for the Licensed Products for which Ionis is responsible in accordance with <u>Article 7</u> (Manufacturing), in each case
                subject to the remainder of this <u>Article 5</u> (Regulatory Affairs) (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#160;<font style="font-weight: bold; font-style: italic;">Regulatory Activities</font>&#8221;). Subject to the
                obligations in this <u>Article 5</u> (Regulatory Affairs), the Regulatory Responsible Party will be responsible for, and [***] all Regulatory Submissions, communications, and other dealings with the Regulatory Authorities relating to the
                Licensed Products in the applicable Territory, and for seeking and maintaining all Regulatory Approvals with respect to the Licensed Product in the applicable Territory. The Regulatory Responsible Party will not be required to delay any
                submission, correspondence, or communication with any Regulatory Authorities in a manner that affects such Regulatory Responsible Party&#8217;s ability to comply with any Regulatory Authority requirement or deadline or Applicable Law in such
                jurisdiction. For clarity, Otsuka or its designee shall be the holder of all Regulatory Approvals for the Licensed Product in the Otsuka Territory and will own all Regulatory Submissions in the Otsuka Territory, and Ionis or its designee
                shall be the holder of all Regulatory Approvals for the Licensed Product in the Ionis Territory and will own all Regulatory Submissions in the Ionis Territory. Otsuka will only [***] and will not [***]. </div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z47e479a973c5401c87e0add1c6d09b63">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Europe Regulatory Subcommittee</font>. The Parties have established a Subcommittee of the Europe JSC to (a) oversee the preparation and submission of any MAA for a Licensed Product in the Europe Territory
                and (b) coordinate the regulatory responsibilities between the Parties in the Europe Territory, which allocation will be consistent with this <u>Article 5</u> (Regulatory Affairs) (such Subcommittee, the &#8220;<font style="font-weight: bold; font-style: italic;">Europe Regulatory Subcommittee</font>&#8221;). The Europe Regulatory Subcommittee will review and comment on any proposed MAA application for a Licensed Product in the Europe Territory sufficiently in advance of the filing
                or submission thereof by Otsuka, and Otsuka will [***] any comments received from the Europe Regulatory Subcommittee. The Europe Regulatory Subcommittee will meet as often as necessary to carry out the activities described in this <u>Section




                  5.2</u> (Europe Regulatory Subcommittee) and the terms of <u>Section 8.3</u> (Subcommittees) will apply to the Europe Regulatory Subcommittee.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">17</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z41a50c02679541dea4866a6d4ea9d528">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Correspondences with Regulatory Authorities</font>. Otsuka shall be solely responsible for communications with Regulatory Authorities in the Otsuka Territory regarding the Licensed Product and in no event
                will [***] regarding the Licensed Product in the Otsuka Territory, except in connection with [***], and subject to the remainder of this <u>Section 5.3</u> (Correspondences with Regulatory Authorities). Ionis will [***]. In addition, Ionis
                will [***]. Furthermore, upon Otsuka&#8217;s reasonable request and at [***], Ionis will [***]. The Regulatory Responsible Party will provide the other Party with (a) copies of any material written correspondence submitted to or received from (i)
                with respect to Otsuka, the EMA, PMDA, or any other Regulatory Authority in the Europe Territory or [***], and (ii) with respect to Ionis, the FDA or any other Regulatory Authority in the U.S., and (b) summaries of any material oral
                communications with such Regulatory Authority in clause (a), in each case ((a) and (b)), relating to Regulatory Submissions in support of Development of the Licensed Products in such jurisdiction or country, reasonably promptly after
                receipt or delivery by such Regulatory Responsible Party of such correspondence or communication, as the case may be (but in any event, no later than [***] after receipt or delivery).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9f36c8f73b984573b9e587eeac944c25">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Regulatory Meetings</font>. Ionis will [***] meetings pertaining to Regulatory Submissions for the Licensed Products relating to the Ionis Regulatory Activities [***] in the Otsuka Territory to the extent
                not prohibited by Applicable Law or the applicable Regulatory Authority. At Otsuka&#8217;s request, Ionis will [***]. With respect to all other meetings with any Regulatory Authority in the Europe Territory or [***] in support of Development of
                the Licensed Products, (a) Ionis will have the right, but not the obligation, [***] to attend such meetings [***] and (b) at Otsuka&#8217;s reasonable request, Ionis will [***] and Otsuka will [***]. Further, Ionis will [***], unless Ionis
                reasonably believes that [***], and will not [***] except as (i) required by Applicable Law, (ii) permitted pursuant to <u>Section 12.4.1(b)</u> (Permitted Circumstances) or <u>Section 12.4.1(c)</u> (Permitted Circumstances), or (iii)
                authorized by Otsuka in writing. For clarity, the terms of this <u>Section 5.4</u> (Regulatory Meetings) will apply solely with respect to any meetings with any Regulatory Authority in the Europe Territory or [***] in support of
                Development of the Licensed Products and do not apply to any other meetings with Regulatory Authorities in the Otsuka Territory, including any meetings pertaining to [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z70bc375d4a714251ba29bf17147f1394">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Regulatory Submissions</font>. Each Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Filing Party</font>&#8221;) will provide the other Party with a copy of [***] (including, [***]) that the
                Filing Party intends to file with or submit to any Regulatory Authority in support of Development in the Otsuka Territory for the other Party&#8217;s review and comment sufficiently in advance of the Filing Party&#8217;s filing or submission thereof; <font style="font-style: italic;">provided</font> that, as it relates to the Asia Territory, Otsuka (a) will [***], (b) will [***], and (c) will [***]. The Filing Party will [***] any reasonable comments received from the other Party into such
                Regulatory Submissions. In addition and notwithstanding <u>Section 3.2</u> (Technology Transfer Costs), Ionis will provide to Otsuka, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za02cda0dc0b945dba4075109cc538853">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.6</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Cooperation</font>. The Parties will cooperate with each other to achieve the regulatory objectives contemplated herein in a timely, accurate, and responsive manner. Without limiting the foregoing or the
                terms of <u>Section 5.5</u> (Regulatory Submissions), at Otsuka&#8217;s reasonable request, Ionis will [***] of the Licensed Products in the Otsuka Territory or for obtaining and maintaining Regulatory Approval of the Licensed Products in the
                Otsuka Territory. Without limiting the foregoing, if requested by any Regulatory Authority in the Asia Territory or [***] for obtaining Regulatory Approvals in the Asia Territory, Ionis will provide to Otsuka (to the extent not prohibited
                by confidentiality obligations to a Third Party) or directly to the applicable Regulatory Authority (to the extent confidentiality obligations to a Third Party prohibit disclosure to Otsuka but permit disclosure to such Regulatory
                Authority) reports and other documents related to other antisense oligonucleotide compounds or products (other than the Licensed Products) being developed by Ionis or any of its Affiliates or Third Party licensees. If Otsuka receives any
                inquiry from a Regulatory Authority in the Otsuka Territory pertaining to any activities for which Ionis is responsible hereunder (including Cross-Territory Clinical Studies, non-clinical or CMC Development or Manufacturing (prior to the
                applicable Manufacturing Handover Date)), then notwithstanding <u>Section 3.2</u> (Technology Transfer Costs), upon Otsuka&#8217;s request, Ionis will, [***]. In addition, upon Otsuka&#8217;s reasonable request, Ionis shall provide [***] in the Otsuka
                Territory (&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Support</font>&#8221;). With respect to the Asia Territory, Regulatory Support includes, and [***] Ionis shall provide, [***]. Ionis will provide all Regulatory Support
                [***] (i) with respect to Regulatory Support related to the Europe Territory, until [***] and (ii) with respect to Regulatory Support related to the Asia Territory, until [***]. Thereafter, (A) [***], Ionis will [***], and [***], Ionis will
                [***] and (B) [***], Ionis will [***], and [***], Ionis will [***]. At all times, Otsuka will [***]. Ionis may [***] for such (1) [***], and (2) [***] and, in each case ((1) and (2)), [***] (and, with respect to [***]) therefor [***].
                [***]. For clarity, if Otsuka requests Regulatory Support in connection with [***], Ionis shall provide such Regulatory Support [***], and Otsuka [***]. Notwithstanding any provision to the contrary, this <u>Section 5.6</u> (Cooperation)
                will not require Ionis to conduct any additional Clinical Trials or generate any additional data or information that is not expressly contemplated by the Cross-Territory Clinical Development Plan or Non-Clinical HAE Development Plans.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">18</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z38560dc843c745feadddefa820314b48">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.7</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Cost of Regulatory Activities</font>. Except to the extent specified otherwise in this <u>Article 5</u> (Regulatory Affairs), each Party will be responsible for all costs and expenses incurred in
                connection with its activities under this <u>Article 5</u> (Regulatory Affairs), including the preparation or maintenance of Regulatory Submissions and Regulatory Approvals with respect to the Licensed Products for which it is responsible,
                including any filing fees and, with respect to Ionis, including all costs and expenses of Ionis Regulatory Activities and all costs and expenses related to the ASMF (if filed) and other regulatory affairs related to Manufacturing of
                Licensed Products, which in each case will be borne solely by Ionis.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4ceefe13befb4afcac358d7c05742294">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.8</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">No Harmful Actions</font>. If [***], then such first Party will have the right to bring such matter to the attention of the JSCs at a joint meeting (or the applicable JSC if such matter pertains only to
                the Europe Territory or the Asia Territory) and the Parties will discuss in good faith to resolve such concern. Without limiting the foregoing and notwithstanding any provision to the contrary in this Agreement, Otsuka will not [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc462d5a6f6ae41f79fc6c278f2054d45">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.9</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Right of Reference</font>. Subject to the rules of the relevant Regulatory Authority and the terms of this Agreement, including <u>Section 4.4.4(b)</u> ([***] by Ionis), each Party hereby grants to the
                other Party a &#8220;Right of Reference,&#8221; as that term is defined in 21 C.F.R. &#167; 314.3(b) (or any successor rule or analogous Applicable Law recognized outside of the United States) to, and a right to copy, access, and otherwise use, all
                information and data relating to the Licensed Products in any Regulatory Submission or Regulatory Approval Controlled by the grantor Party during the Term (including, with respect to the grant to Otsuka, a right of reference to Ionis&#8217; Drug
                Master File and ASMF, if filed), solely for the other Party&#8217;s or its Affiliates&#8217; use in the Development or Commercialization of the Licensed Products in the other Party&#8217;s Territory in accordance with this Agreement. All such information and
                data contained in any such Regulatory Submissions or Regulatory Approvals will be considered Confidential Information of the grantor Party and subject to the terms of <u>Article 12</u> (Confidentiality). If requested by the grantee Party,
                the grantor Party will provide a signed statement to this effect in accordance with 21 C.F.R. &#167; 314.50(g)(3) (or any successor rule or analogous Applicable Law outside of the United States) to give effect to the intent of this <u>Section
                  5.9</u> (Right of Reference).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">19</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zdb738022ec34485cb92d5fdf6a6eb537">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.10</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Pharmacovigilance; Safety Information</font>. Each Party will cooperate with the other Party, at no cost to the other Party (notwithstanding <u>Section 3.2</u> (Technology Transfer Costs)), with regard
                to the reporting and handling of safety information involving the Licensed Products in accordance with Applicable Law, regulatory requirements, and regulations on pharmacovigilance and clinical safety. Otsuka will be responsible for all
                processing of information related to any adverse events for the Licensed Products in the Otsuka Territory and Ionis will be responsible for all processing of information related to any adverse events for the Licensed Products in the Ionis
                Territory, in each case, including any information regarding such adverse events that is received from a Third Party. Each Party will provide to the other Party in a timely manner the relevant safety information it receives (either directly
                or indirectly) related to the Licensed Products. At an appropriate time as agreed upon by the Parties following the Restatement Date, but in any event prior to the [***], the Parties will negotiate in good faith and enter into a
                Pharmacovigilance Agreement related to the Licensed Products, which will define the pharmacovigilance responsibilities of the Parties and include safety data exchange procedures governing the exchange of information affecting the class and
                products (<font style="font-style: italic;">e</font>.<font style="font-style: italic;">g</font>., Serious Adverse Events, emerging safety issues) to enable each Party to comply with all of its legal and regulatory obligations related to
                such Licensed Product. Prior to the execution of the Pharmacovigilance Agreement, each Party will have the right, upon reasonable notice to the other Party, to [***]. Ionis will own and maintain the global safety database for the Licensed
                Products at [***], <font style="font-style: italic;">provided</font> that at Otsuka&#8217;s reasonable request, Ionis will run queries of such global safety database and will provide copies of the data contained in such global safety database to
                the extent necessary or reasonably useful to the Development and Commercialization of the Licensed Product in the Otsuka Territory. As part of the negotiation of the Pharmacovigilance Agreement, the Parties will [***], taking into account
                that Ionis will own and maintain the global safety database, and the Parties&#8217; determination of such matter will be set forth in the Pharmacovigilance Agreement. Subject to compliance with Applicable Law, each Party hereby agrees to comply
                with its respective obligations under the Pharmacovigilance Agreement as the Parties may agree to modify it from time to time, and to cause its (sub)licensees to comply with such obligations. If there is a conflict between the terms and
                conditions of this Agreement and any terms and conditions of the Pharmacovigilance Agreement, then the terms and conditions of the Pharmacovigilance Agreement will govern with respect to any pharmacovigilance matters and this Agreement will
                govern with respect to any other matters.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z2a82283f7f1a4071ba3fdf1b161217ca">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.11</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Pharmacovigilance Subcommittee</font>. As of the Restatement Date, the Parties have established a joint pharmacovigilance subcommittee (the &#8220;<font style="font-weight: bold; font-style: italic;">PV
                  Subcommittee</font>&#8221;) that will be a Subcommittee of the Executive Committee. In addition to any other matters that the Executive Committee or JSCs may delegate to the PV Subcommittee, the PV Subcommittee shall provide a forum for the
                Parties to discuss, share information, and escalate and attempt to resolve safety issues regarding the Licensed Product, and any other pharmacovigilance matters, worldwide. The PV Subcommittee will meet as often as necessary to carry out
                such activities, and the terms of <u>Section 8.3</u> (Subcommittees) will apply to the PV Subcommittee.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">20</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb63f3ed4ec344908afce10862c56d0cf">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.12</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ionis Internal Oligonucleotide Safety Database</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z511d800d2026487aa0b285f00bd0adcb">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">5.12.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis maintains an internal database that includes information regarding the tolerability of its drug compounds, individually and as a class, including information discovered during non-clinical and clinical Development (the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Internal Oligonucleotide Safety Database</font>&#8221;). To maximize understanding of the safety profile and pharmacokinetics of Ionis compounds, (a) Ionis will have the right to use any
                safety-related information provided by Otsuka pursuant to the Pharmacovigilance Agreement or this <u>Section 5.12</u> (Ionis Internal Oligonucleotide Safety Database) to maintain the Ionis Internal Oligonucleotide Safety Database and (b)
                Otsuka will cooperate, at no cost to Ionis, with Ionis&#8217; reasonable requests in connection with populating the Ionis Internal Oligonucleotide Safety Database, including by providing Ionis with reasonably requested safety-related supporting
                data and answering any follow-up questions reasonably requested by Ionis or its Affiliates in connection with any information provided under the Pharmacovigilance Agreement, in each case to the extent such data and answers are reasonably
                available to Otsuka. In addition, with respect to Clinical Trials of the Licensed Products conducted by or on behalf of Otsuka pursuant to the Otsuka Territory-Specific Development Plans, Otsuka will provide Ionis with copies of annual
                safety updates filed with each IND and the safety sections of any final Clinical Trial reports within [***] following the date such information is filed, as applicable. All such information disclosed by Otsuka to Ionis will be Otsuka
                Confidential Information; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that so long as Ionis does not disclose the identity of a Licensed Product or Otsuka&#8217;s identity, Ionis may
                disclose any such Otsuka Confidential Information to (i) Ionis&#8217; other partners if such information is regarding class generic properties of oligonucleotides, (ii) any Third Party that contributes to the populating of the Ionis Internal
                Oligonucleotide Safety Database, or (iii) any Regulatory Authority. Otsuka will also cause its Affiliates and Sublicensees to comply with this <u>Section 5.12</u> (Ionis Internal Oligonucleotide Safety Database).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z13533ef4b01243caa2348cfca4bbd65a">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">5.12.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>From time to time, Ionis utilizes the information in the Ionis Internal Oligonucleotide Safety Database to conduct analyses to keep Ionis and its partners informed regarding class generic properties of oligonucleotides, including with
                respect to safety. As such, if and when Ionis identifies safety or other related issues that may be relevant to a Licensed Product (including any potential class-related toxicity), Ionis will promptly inform Otsuka of such issues and
                provide the data supporting Ionis&#8217; conclusions.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1f8780b8765247988178a90254eebce1">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.13</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Recall, Withdrawal, or Field Alerts</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1c008e38bcf64b258cf474d5f573b82c">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">5.13.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Notification and Determination</font>. Each Party will notify the other Party immediately, and promptly confirm such notice in writing, if it obtains information indicating that any Licensed Product may
                be subject to a recall (whether voluntary or mandated), corrective action, or similar regulatory action by any Governmental Authority or Regulatory Authority (a &#8220;<font style="font-weight: bold; font-style: italic;">Remedial Action</font>&#8221;).
                The Parties will assist each other in gathering and evaluating such information as is necessary to determine the necessity of conducting a Remedial Action with respect to the applicable Territory, and otherwise reasonably cooperate with
                each other with respect to such Remedial Action or potential Remedial Action. Ionis will have sole discretion and final decision-making authority with respect to, and control over, any Remedial Action in the Ionis Territory, including any
                decision to commence such Remedial Action in the Ionis Territory. Otsuka will have sole discretion and final decision-making authority with respect to, and control over, any Remedial Action in the Otsuka Territory, including any decision to
                commence such Remedial Action in the Otsuka Territory; <font style="font-style: italic;">provided that </font>if Ionis notifies Otsuka of [***] that Ionis reasonably believes could give rise to a Remedial Action in the Otsuka Territory
                (or applicable Region), then Otsuka will initiate such Remedial Action in accordance with Ionis&#8217; request and at [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8836b750ee1246c2880c3392e5484acb">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">5.13.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Cost Allocation</font>. Except as otherwise set forth in <u>Section 5.13.1</u> (Notification and Determination), all costs directly associated with implementing a Remedial Action with respect to a
                Licensed Product will be allocated between Ionis and Otsuka as follows:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze9765cd268ef40dd82bbd84746cacf16">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>If, and to the extent, that the Remedial Action arises as a result of [***], then [***] will bear all such costs and expenses; and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z17fab049b0f847f9b1200d18225647b2">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>in all other cases, Ionis will be responsible for such costs and expenses for such Licensed Product in the Ionis Territory and Otsuka will be responsible for such costs and expenses for such Licensed Product in the Otsuka Territory.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">21</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
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      </div>
      <div style="text-align: center; font-weight: bold;">ARTICLE 6</div>
      <div style="text-align: center; font-weight: bold;">COMMERCIALIZATION AND MEDICAL AFFAIRS</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z81035d6793cf4eb9a7383a4d646ea551">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Commercialization Responsibilities for Licensed Product</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z368182c1d37b451fa72a6fa91f76f846">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">6.1.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Commercialization in the Ionis Territory</font>. Subject to the last sentence of <u>Section 6.4.1</u> (Global Brand Strategy and American Commercialization Operating Plan) and the last sentence of <u>Section




                  6.6.1</u> (Global Medical Affairs Strategy and American Medical Affairs Operating Plan), and without limiting Ionis&#8217; obligations under this <u>Article 6</u> (Commercialization and Medical Affairs), Ionis and its Affiliates will have
                [***] with respect to the Commercialization of the Licensed Products in the Ionis Territory, including, if applicable, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9d9d5700341e49179394c9d92c1ea3f6">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">6.1.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Commercialization in the Otsuka Territory</font>. Subject to the terms and conditions of this Agreement, and without limiting Otsuka&#8217;s obligations under this <u>Article 6</u> (Commercialization and
                Medical Affairs), Otsuka and its Affiliates will have [***] with respect to the Commercialization of the Licensed Products in the Otsuka Territory, including [***]. Upon Otsuka&#8217;s reasonable request, Ionis shall [***], including [***], and
                Ionis will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze23f816aee2043c583c9e7c46abcafdd">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">6.1.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Coordination of Commercialization Activities</font>.<font style="font-weight: bold;">&#160;</font>The Parties will coordinate global Commercialization activities with respect to Commercialization of the
                Licensed Products in each Party&#8217;s Territory through the JSCs, as further set forth in <u>Section 8.2</u> (Joint Steering Committees) and this <u>Article 6</u> (Commercialization and Medical Affairs).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf574faa6e4d74ecfaa57f814810d6bff">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Commercialization and Medical Affairs Reporting</font>. At each Europe JSC meeting following the first Regulatory Approval for a Licensed Product in the Europe Territory and at each Asia JSC meeting
                following the first Regulatory Approval for a Licensed Product in [***], Otsuka will provide to the applicable JSC a high-level summary (which may be in the form of a slide presentation) of the material Commercialization and Medical Affairs
                activities conducted by Otsuka or its Affiliates or Sublicensees for the Licensed Products in the Europe Territory or [***], as applicable, during the period since the last applicable JSC meeting and the material Commercialization and
                Medical Affairs activities expected to be conducted by Otsuka or its Affiliates, or Sublicensees in the Europe Territory or [***], as applicable, for the Licensed Products during the period from the date of such update until the next
                applicable JSC meeting, and shall answer any reasonable questions asked by Ionis to enable Ionis to assess Otsuka&#8217;s compliance with its Commercialization diligence obligations set forth in <u>Section 6.5</u> (Otsuka Commercialization
                Diligence Obligations). In addition, no later than [***], Otsuka will provide to the Europe JSC or the Asia JSC, as applicable, a report of the forecasted Net Sales anticipated to be generated by Otsuka or its Affiliates, licensees, or
                Sublicensees in the Europe Territory or [***], as applicable, during the upcoming Calendar Year, which forecast will be broken down on a country-by-country basis. At each Europe JSC meeting following the first Regulatory Approval for a
                Licensed Product in the Ionis Territory, Ionis will provide to the Europe JSC a high-level summary (which may be in the form of a slide presentation) of the material Commercialization and Medical Affairs activities conducted by Ionis or its
                Affiliates for the Licensed Products in the Ionis Territory during the period since the last Europe JSC meeting and the material Commercialization and Medical Affairs activities expected to be conducted by Ionis or its Affiliates in the
                Ionis Territory for the Licensed Products during the period from the date of such update until the next Europe JSC meeting. Without limiting the foregoing, at Otsuka&#8217;s reasonable request, Ionis will provide to Otsuka, [***], all information
                relating to the [***]. In addition, Otsuka will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">22</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6b6ab9f5bfec4571b5b004531b8a41b5">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Pricing</font>. All decisions for the Licensed Products related to list price, targeted net pricing, sales-weighted average discounts and rebates, pricing strategy (including the approach to pricing with
                different types of accounts and plans, including types of discounts and rebates), and modifications to any of the foregoing, will be made by (a) Ionis in the Ionis Territory and (b) Otsuka in the Otsuka Territory; <font style="font-style: italic;">provided </font>that, [***<font style="color: rgb(0, 0, 0);">]</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5827f04dd7f44436969f0bf833368bd4">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-weight: bold;">Brand Strategy and Operating Plans.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1c380ed5c8834403bc7102313b3b5c92">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">6.4.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Global Brand Strategy and American Commercialization Operating Plan</font>. Prior to the Restatement Date, Ionis developed and [***], a global brand strategy for the Commercialization of the Licensed
                Products throughout the Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Global Brand Strategy</font>&#8221;) and an operating plan with respect to Commercialization activities in the U.S. (the &#8220;<font style="font-weight: bold; font-style: italic;">American Commercialization Operating Plan</font>&#8221;). The Global Brand Strategy and the American Commercialization Operating Plan shall at all times conform to applicable Professional Requirements and Applicable Law
                (including compliance requirements). Ionis, through the Europe JSC, will update the Global Brand Strategy and the American Commercialization Operating Plan [***]. In addition, [***], either Party may propose material updates or
                modifications to the Global Brand Strategy and Ionis may propose material updates to the American Commercialization Operating Plan to [***]. No update or modification to the Global Brand Strategy or to the American Commercialization
                Operating Plan will be effective unless and until [***]. Once [***], such updated version of the Global Brand Strategy or the American Commercialization Operating Plan will automatically become effective and replace the then-prior version
                of the Global Brand Strategy or the American Commercialization Operating Plan, as applicable. The Global Brand Strategy will include, in reasonable detail, the Trademarks to be used by the Parties or its Affiliates or its or their
                Sublicensees for the Commercialization of Licensed Product, trade dress, positioning, market access strategy, and marketing strategic imperatives, objectives and messaging with respect to the Licensed Products.<font style="font-style: italic;">&#160;</font>At Otsuka&#8217;s reasonable request, Ionis will provide to Otsuka, [***]. Ionis will, [***], lead and conduct all Commercialization activities for the Licensed Products in the Ionis Territory [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">23</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z57f7be3e1e8e45f594eddae519d411fa">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">6.4.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Territory Brand Strategy and Commercialization Operating Plans</font>. Within [***] after the date [***] approves the initial Global Brand Strategy and the initial American Commercialization
                Operating Plan, Otsuka will prepare and submit to [***] a brand strategy for the Commercialization of the Licensed Products in the Europe Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Europe Territory Brand Strategy</font>&#8221;)




                and an operating plan with respect to the Commercialization of the Licensed Products in the Europe Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Europe Territory Commercialization Operating Plan</font>&#8221;). If Otsuka&#8217;s
                brand strategy for the Commercialization of the Licensed Products in any country in the Asia Territory will be materially inconsistent with the Global Brand Strategy, then, [***], Otsuka will prepare and submit to [***] a brand strategy for
                the Commercialization of the Licensed Products in such country in the Asia Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Asia Territory Brand Strategy</font>,&#8221; and together with the Europe Territory Brand Strategy,
                the &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory Brand Strategy</font>&#8221;). For clarity, Otsuka shall not be required to prepare or submit to [***] any brand strategy with respect to the Commercialization of the
                Licensed Products in any country in the Asia Territory unless such strategy for such country is materially inconsistent with the Global Brand Strategy. [***], Otsuka will prepare and submit to [***] an operating plan with respect to the
                Commercialization of the Licensed Products in [***] (each such plan for [***], the &#8220;<font style="font-weight: bold; font-style: italic;">Asia Territory Commercialization Operating Plan</font>,&#8221; and together with the Europe Territory
                Commercialization Operating Plan, the &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory Commercialization Operating Plans</font>&#8221;). [***] will review, discuss, and determine whether to approve the initial Europe
                Territory Brand Strategy and the initial Europe Territory Commercialization Operating Plan and [***] will review, discuss, and determine whether to approve each initial Asia Territory Brand Strategy (if any) and each initial Asia Territory
                Commercialization Operating Plan. Each Otsuka Territory Brand Strategy will, at all times during the Term, be consistent with the then-current Global Brand Strategy, except to the extent such inconsistency is (i) necessary to (A) conform
                with any written requirement from any Regulatory Authority or with any Applicable Law or Professional Requirements in the Europe Territory or the Asia Territory, as applicable, or (B) avoid infringement of a Third Party Trademark in the
                Europe Territory or Asia Territory, as applicable, or (ii) approved by the applicable JSC or Executive Committee (by unanimous Party Vote). On [***] during the Term (and more frequently as may be necessary), Otsuka will prepare an update to
                each Otsuka Territory Brand Strategy and each Otsuka Territory Commercialization Operating Plan. [***] will review, discuss, and determine whether to approve each update to the Europe Territory Brand Strategy and each update to the Europe
                Territory Commercialization Operating Plan and [***] will review, discuss, and determine whether to approve each update to each Asia Territory Brand Strategy and each update to each Asia Territory Commercialization Operating Plan. Once
                approved by [***], the applicable Otsuka Territory Brand Strategy and the applicable Otsuka Territory Commercialization Operating Plan will automatically become effective and, in the case of an update, will supersede the applicable previous
                Otsuka Territory Brand Strategy and the applicable previous Otsuka Territory Commercialization Operating Plan as of the date of such approval by [***]. Otsuka will, at its cost and expense, lead and conduct all Commercialization activities
                in the Otsuka Territory [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfa5f94d51c34464cba72ba7088aa02e7">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Commercialization Diligence Obligations</font>. On a country-by-country basis in the Otsuka Territory, following [***], Otsuka will use Commercially Reasonable Efforts to obtain Reimbursement
                Approval for and otherwise Commercialize such Licensed Product in such country.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z28ff5e4799df44f095ef02ff568e07ad">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.6</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="color: rgb(0, 0, 0); font-weight: bold;">Medical Affairs Plans.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc45872dad9e845578999b163198b8d4a">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">6.6.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Global Medical Affairs Strategy and American Medical Affairs Operating Plan</font><font style="font-weight: bold; color: rgb(0, 0, 0);">. </font><font style="color: rgb(0, 0, 0);">Prior to the
                  Restatement Date, Ionis developed and [</font>***<font style="color: rgb(0, 0, 0);">], </font>a plan for the global Medical Affairs activities for the Licensed Products throughout the Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Global Medical Affairs Strategy</font>&#8221;) and an operating plan with respect to Medical Affairs activities in the U.S. (the<font style="font-weight: bold; font-style: italic;">&#160;</font><font style="font-weight: bold;">&#8220;</font><font style="font-weight: bold; font-style: italic;">American Medical Affairs Operating Plan</font>&#8221;). The Global Medical Affairs Strategy and the American Medical Affairs Operating Plan shall at all times conform to applicable Professional
                Requirements and Applicable Law (including compliance requirements) with adjustments with respect to the Global Medical Affairs Strategy as necessary to comply with local Applicable Law and Professional Requirements in the Otsuka Territory.
                Ionis, through the Europe JSC, will update the Global Medical Affairs Strategy and the American Commercialization Operating Plan on [***] basis. In addition, between [***] updates, either Party may propose material updates or modifications
                to the Global Medical Affairs Strategy and Ionis may propose material updates or modifications to the American Medical Affairs Operating Plan [***]. No update or modification to the Global Medical Affairs Strategy or the American Medical
                Affairs Operating Plan will be effective unless and until approved by [***]. Once approved by [***], such updated version of the Global Medical Affairs Strategy or the American Medical Affairs Operating Plan will become effective and
                replace the then-prior version of the Global Medical Affairs Strategy or American Medical Affairs Operating Plan. Ionis will, at its cost and expense, lead and conduct all Medical Affairs activities for the Licensed Products in the Ionis
                Territory [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">24</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf1f9cd8476ea47f58d92149a53cdeae3">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">6.6.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Territory Medical Affairs Plans</font><font style="font-weight: bold; color: rgb(0, 0, 0);">. </font><font style="color: rgb(0, 0, 0);">Within [</font>***<font style="color: rgb(0, 0, 0);">] after
                  the date [</font>***<font style="color: rgb(0, 0, 0);">] approves </font>the initial Global Medical Affairs Strategy and the initial American Medical Affairs Operating Plan, Otsuka will prepare and submit to [***] a plan for the Medical
                Affairs activities for the Licensed Products in the Europe Territory (such plan, the &#8220;<font style="font-weight: bold; font-style: italic;">Europe Territory Medical Affairs Plan</font>&#8221;). [***], Otsuka will prepare and submit to [***] a plan
                for the Medical Affairs activities for the Licensed Products in [***] (each such plan for [***], the &#8220;<font style="font-weight: bold; font-style: italic;">Asia Territory Medical Affairs Plan</font>,&#8221; and together with the Europe Territory
                Medical Affairs Plan, the &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory Medical Affairs Plans</font>&#8221;). [***] will review, discuss, and determine whether to approve the initial Europe Territory Medical Affairs Plan
                and [***] will review, discuss, and determine whether to approve the initial Asia Territory Medical Affairs Plan. Each Otsuka Territory Medical Affairs Plan will, at all times during the Term, be consistent with the then-current Global
                Medical Affairs Strategy, except to the extent such inconsistency is (i) necessary to conform with any written requirement from any Regulatory Authority or with any Applicable Law or Professional Requirements in the Europe Territory or the
                Asia Territory, as applicable, or (ii) approved by the applicable JSC or Executive Committee (by unanimous Party Vote). On [***] during the Term (and more frequently as may be necessary), Otsuka will prepare an update to each Otsuka
                Territory Medical Affairs Plan. [***] will review, discuss, and determine whether to approve each update to the Europe Territory Medical Affairs Plan and [***] will review, discuss, and determine whether to approve each update to the Asia
                Territory Medical Affairs Plan. Once approved by [***], the applicable Otsuka Territory Medical Affairs Plan will automatically become effective and, in the case of an update, supersede the previous Otsuka Territory Medical Affairs Plan as
                of the date of such approval by [***]. Otsuka will, at its cost and expense, lead and conduct all Medical Affairs activities in the Otsuka Territory [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z55297557949345e68b1a8e5a3c394fd6">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.7</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Standards of Conduct; Compliance</font>. Each Party will perform, or will ensure that each of its Affiliates, Sublicensees, and Subcontractors perform, all Commercialization and Medical Affairs activities
                in a professional and ethical business manner and in compliance with Applicable Law and applicable Professional Requirements.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z91eee13b6f5642d6be742773204d49dc">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.8</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Product Materials</font>. Each Party will, at its cost and expense, be responsible for preparing, developing, producing, or otherwise obtaining, and utilizing promotional materials, training materials,
                medical education materials, Packaging and Labeling, and all other literature or other information related to the Licensed Products<font style="font-weight: bold;"> (&#8220;</font><font style="font-weight: bold; font-style: italic;">Product
                  Materials</font><font style="font-weight: bold;">&#8221;) to support its Commercialization and </font>Medical Affairs <font style="font-weight: bold;">activities in such Party&#8217;s Territory, which Product Materials will at all times [</font>***<font style="font-weight: bold;">]. From time to time, and in any event upon Otsuka&#8217;s request, Ionis will share with Otsuka samples of Product Materials Controlled by Ionis and which are used by Ionis, its Affiliates, or licensees in connection
                  with the Commercialization of or conduct of </font>Medical Affairs activities for<font style="font-weight: bold;"> the Licensed Products. From time to time, and in any event upon Ionis&#8217; request, Otsuka will share with Ionis samples of
                  Product Materials Controlled by Otsuka and which are used by Otsuka, its Affiliates or sublicensees in connection with the Commercialization of or conduct of </font>Medical Affairs activities<font style="font-weight: bold;"> the Licensed
                  Products in the Otsuka Territory.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">25</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb0a2e1658ba34564bb8039588e74b6b7">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.9</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Diversion</font>. Neither Party nor its Affiliates will, and each Party will take reasonable measures to ensure that its Sublicensees, licensees, and Subcontractors do not, either directly or to such
                Party&#8217;s knowledge, intentionally indirectly,<font style="font-weight: bold; font-style: italic;">&#160;</font>promote, market, distribute, import, sell, or have sold any Licensed Product to any Third Party or to any address or Internet Protocol
                address or the like outside of such Party&#8217;s Territory including via the Internet or mail order. Notwithstanding any provision to the contrary set forth in this Agreement, [***]. As applicable, (i) in the case of Otsuka, in any country or
                jurisdiction outside of the Otsuka Territory, and (ii) in the case of Ionis, in any country or jurisdiction outside of the Ionis Territory:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z46712cbab01d4e2eb945fe5346c4e75e">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">6.9.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>such Party and its Affiliates will not engage, nor permit its Sublicensees, licensees, and Subcontractors to engage, in any advertising or promotional activities relating to any Licensed Product for use directed primarily to customers or
                other buyers or users of the Licensed Products located in any such country or jurisdiction;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z73f8166753e24024b2bafaaa7d01ee92">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">6.9.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>such Party and its Affiliates will not solicit orders of the Licensed Products from any prospective purchaser located in any such country or jurisdiction;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze8dc5f895cc740728870b09e5f02df73">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">6.9.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>such Party and its Affiliates will not, and will <font style="color: rgb(0, 0, 0);">take reasonable measures to </font>cause its Sublicensees, licensees and Subcontractors to not, deliver or tender (or cause to be delivered or
                tendered) any Licensed Product to Third Parties for use in such country or jurisdiction; and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zdac1ca51a27c46edbf26ac690e9d5861">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">6.9.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>if either Party or its Affiliates, Sublicensees, or licensees receive any order for any Licensed Product from a prospective purchaser located in any such country or jurisdiction, then such Party will immediately refer that order to the
                other Party or its designee and will not accept any such orders.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">ARTICLE 7</div>
      <div style="text-align: center; font-weight: bold;">MANUFACTURING</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3e42def929c44c42aa33b8b696110be5">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Responsibility</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0727f3ef2ea1469196d24ffc79c42073">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">7.1.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ionis Manufacturing</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7eb8fd6a93654a86b3c8486032f70343">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ionis Territory</font>. Ionis will have sole control over and decision-making authority with respect to, at its cost and expense, the Manufacture of (i) all supplies of the Licensed Products required for
                Ionis&#8217; activities under the Cross-Territory Clinical Development Plan and the Non-Clinical HAE Development Plans, and for all Development activities in the Ionis Territory and (ii) all supplies of the Licensed Products for Commercialization
                purposes in the Ionis Territory.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z868370cbb99441a087bd9c9326ffee8d">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Europe Territory</font>. Subject to the remainder of this <u>Section 7.1.1(b)</u> (Europe Territory) and <u>Section 7.1.2</u> (Otsuka Manufacturing), in accordance with the Supply Agreements and Quality
                Agreements, Ionis will Manufacture and supply Otsuka with all Licensed Product that is necessary for Otsuka to (i) [***] and (ii) [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze05cb923efae434284ace84702117875">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Asia Territory</font>. Subject to the remainder of this <u>Section 7.1.1(c)</u> (Asia Territory) and <u>Section 7.1.2</u> (Otsuka Manufacturing), in accordance with the Supply Agreements and Quality
                Agreements, Ionis will Manufacture and supply Otsuka with all Licensed Product that is necessary for Otsuka to (i) [***] and (ii) [***]. Notwithstanding the foregoing, on a country-by-country basis in the Asia Territory, (A) if required by
                Applicable Law, any Regulatory Authority or the conditions and requirements of Regulatory Approvals in such country in the Asia Territory, Ionis will [***], or (B) if mutually agreed by the Parties (such agreement not to be unreasonably
                withheld, conditioned or delayed), Ionis will [***], <font style="font-style: italic;">provided that</font>, in each case ((A) and (B)), [***]. Notwithstanding any provision to the contrary in this Agreement, Ionis will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">26</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7672bc654f18479a907f03091f95916c">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(d)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Support</font>. Upon Otsuka&#8217;s reasonable request prior to the applicable Manufacturing Handover Date, Ionis will provide (or will use commercially reasonable efforts to cause its CMOs to provide) to
                Otsuka (i) [***], (ii) [***], and (iii) [***], in each case ((i) &#8211; (iii)), to the extent [***]. Ionis will provide all such Requested Assistance to Otsuka in accordance with the terms of <u>Section 3.2</u> (Technology Transfer Costs) and
                will provide such data and information to Otsuka [***]. For clarity, and notwithstanding anything to the contrary herein, Ionis will provide to the Qualified Person for the Licensed Products in the Europe Territory, [***], Manufacturing
                audit or inspection reports as required under EU GMP, Annex 16, section 2.2 for the purposes of batch certification in the Europe Territory.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z663fc5b5478841a3beb9f4c9a923aa2e">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">7.1.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Manufacturing</font>. [***], Otsuka will have the right to assume responsibility for Manufacturing (a) all supplies of the Licensed Products required for Otsuka&#8217;s activities under the Otsuka
                Territory-Specific Development Plans in [***] the Otsuka Territory and (b) all supplies of the Licensed Products for Commercialization purposes in [***] the Otsuka Territory, in each case, upon written notice to Ionis at any time after the
                earliest of (i) [***], (ii) [***], and (iii) [***] (such notice [***], the &#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Handover Notice</font>&#8221; [***]). If Otsuka provides Ionis with a Manufacturing Handover Notice
                [***], then Ionis&#8217; obligations to Manufacture and supply Otsuka in accordance with <u>Section 7.1.1</u> (Ionis Manufacturing) will terminate [***], following the completion of all activities under the Manufacturing Technology Transfer
                Agreement in accordance with <u>Section 7.4</u> (Manufacturing Technology Transfer) [***], and the initiation of actual Manufacturing of the Licensed Products to be sold by or on behalf of Otsuka [***] at Otsuka&#8217;s or its designee&#8217;s
                manufacturing facility (such date [***], the &#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Handover Date</font>&#8221; [***]).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z45593f77edfd4c73b4e4792a959cb329">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Supply and Quality Agreements; Manufacturing Costs</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0aa72eb3d5a946b2b3880b063265b23c">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">7.2.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Clinical Supply Agreement</font>. Unless otherwise agreed by the Parties, within a timeframe following the Restatement Date to be agreed by the Parties,<font style="font-weight: bold; font-style: italic;">&#160;</font>the




                Parties will negotiate in good faith and enter into a supply agreement on reasonable and customary terms for the supply of Licensed Products by Ionis to Otsuka for clinical use (the &#8220;<font style="font-weight: bold; font-style: italic;">Clinical




                  Supply Agreement</font>&#8221;), which agreement (together with the related Quality Agreement) will govern the terms and conditions of the Manufacture and supply of the Licensed Products for Development purposes in the Otsuka Territory. Otsuka
                will pay a supply price to Ionis under the Clinical Supply Agreement equal to [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">27</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z94aedf49cbf94e3d8c613d821d8fcc7d">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">7.2.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Commercial Supply Agreement</font>. Within a timeframe following the Restatement Date to be agreed by the Parties, the Parties will negotiate in good faith and enter into a commercial supply agreement on
                reasonable and customary terms for the commercial-grade supply of Licensed Products by Ionis to Otsuka (the &#8220;<font style="font-weight: bold; font-style: italic;">Commercial Supply Agreement</font>&#8221; and together with the Clinical Supply
                Agreement, the &#8220;<font style="font-weight: bold; font-style: italic;">Supply Agreements</font>&#8221;), which agreement (together with the related Quality Agreement) will govern the terms and conditions of the Manufacture and supply of the
                Licensed Products for Commercialization purposes in the Otsuka Territory. Otsuka will pay a supply price to Ionis under the Commercial Supply Agreement equal to [***]. The Commercial Supply Agreement shall allow Otsuka to order, and Ionis
                to supply, a portion of a batch as the minimum order quantity, as further detailed in such Commercial Supply Agreement; <font style="font-style: italic;">provided</font> that [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8a8f357a9e124edca21e0377b2d75cbe">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">7.2.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Quality Agreements</font>. The Parties will negotiate in good faith and enter into one or more quality technical agreements pertaining to clinical and commercial supply of Licensed Products to Otsuka
                (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Quality Agreement</font>&#8221;) containing reasonable and customary terms and conditions regarding quality assurance, quality control, compliance with GMP, GDP and GCP (as
                applicable), specifications, change control procedures, and provisions relating to audits and inspections. If Otsuka is required by Regulatory Authority or Applicable Law in any country in the Asia Territory to enter into a Quality
                Agreement directly with a CMO that Manufactures Licensed Product (including drug substance (API) and bright stock or finished Licensed Product) for Commercialization in such country, then the Parties will [***]. If there are terms or
                conditions that are required to be in a quality agreement by Applicable Law or a Regulatory Authority in the Asia Territory but that are inconsistent with an existing quality agreement between Ionis and its CMO, Ionis will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd34a5cbfb5264588a25bdefadc011dfd">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">7.2.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Manufacturing Cost Increases</font>. If the Manufacturing Costs, whether for clinical or commercial supplies of Licensed Product, are reasonably anticipated to increase, on a per unit basis, such that the
                [***], then Ionis will provide prompt written notice to Otsuka of such increase. If such increase is anticipated to result in [***], on a per unit basis, then [***]. If such increase is anticipated to result in [***] on a per unit basis,
                then [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc591ace8a27940fa9c491e715d2866f7">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">7.2.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Capital Expenditures</font>. Ionis [***]. In addition, if any CMO requests or requires [***], then Ionis will notify Otsuka and the Parties will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z42368a3c19a34e5886b62f6def28dd2e">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">7.2.6</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">[</font>***<font style="font-weight: bold;">]</font>. If the reasonable allocation of [***], then [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3214452c5daa44ffb60c4542e92f8cbb">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">&#160;Audits and Inspections</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z02826cf80490423ea744eb97a7960876">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">7.3.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">By Otsuka</font>. Prior to execution of the first Quality Agreement, Otsuka shall be entitled to conduct [***]. In addition, if Ionis elects to inspect or audit any facilities of its CMOs with respect to
                the Manufacture of Licensed Products for the Otsuka Territory, Ionis shall notify Otsuka of such inspection or audit and, [***]. In addition, to the extent permitted under Ionis&#8217; agreement with the applicable CMO and subject to any
                conditions set forth in such agreement with respect to any inspection or audit (<font style="font-style: italic;">e.g.</font>, an obligation to enter into a confidentiality agreement with the applicable CMO), Ionis shall [***]. If Otsuka
                identifies the need to perform a &#8220;for cause&#8221; audit of such facilities to address quality or compliance issues related to any Licensed Product Manufactured for the Otsuka Territory (including to address any notice from a Governmental
                Authority in the Otsuka Territory of noncompliance with Applicable Laws), as well as in connection with the preparation of Regulatory Submissions for the Otsuka Territory and in response to Regulatory Authority requirements in the Otsuka
                Territory, then Otsuka shall notify Ionis and if Ionis agrees with Otsuka&#8217;s determination that a &#8220;for cause&#8221; audit is needed, Ionis will schedule and conduct such audit and Otsuka will [***], in each case, to the extent permitted pursuant
                to the applicable agreement with the applicable CMO.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">28</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb471ca4e2bde4ef59cdac16d4b76d220">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">7.3.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">By Governmental Authority</font>. If any Governmental Authority carries out or gives notice of its intention to carry out any inspection or audit of any of Ionis&#8217; CMOs in relation to Manufacture of
                Licensed Products for the Otsuka Territory and Ionis is aware of such upcoming inspection or audit, then Ionis shall promptly notify Otsuka thereof and Ionis shall, to the extent permitted by its agreement with the applicable CMO and the
                applicable Governmental Authority, [***]. Following receipt by Ionis of the inspection results or audit observations of the Governmental Authority from such inspection or audit (a redacted copy of which Ionis will promptly provide to Otsuka
                to the extent it relates to Licensed Products Manufactured for the Otsuka Territory), Ionis will (a) prepare any appropriate responses and (b) provide a copy of such responses to Otsuka [***] in advance of the date such responses are due,
                to the extent such responses pertain to the Manufacture of Licensed Products for the Otsuka Territory, and Ionis shall [***], in each case ((a) and (b)), to the extent permitted under Ionis&#8217; agreement with such CMOs and subject to any
                conditions set forth in the applicable agreement with such CMOs with respect to any inspection or audit (<font style="font-style: italic;">e.g.</font>, an obligation to enter into a confidentiality agreement with the applicable CMO).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4e1b88bd4e8d4d3e8fc97fc9380c07c2">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">7.3.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">CMO Agreements</font>.<font style="font-weight: bold;">&#160;</font>Ionis shall [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4aee95bbfbe2473c8f78049dc86ee1ae">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Manufacturing Technology Transfer</font>. At Otsuka&#8217;s request any time after Otsuka provides a Manufacturing Handover Notice [***], Ionis will make available to Otsuka all Ionis Manufacturing and
                Analytical Know-How and materials (the &#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Technology Transfer</font>&#8221;) for [***]. Otsuka will (a) use Ionis Manufacturing and Analytical Know-How and materials provided by
                Ionis in connection with the Manufacturing Technology Transfer only in the fulfillment of obligations or exercise of rights under this Agreement, and (b) not transfer such Ionis Manufacturing and Analytical Know-How or materials or deliver
                the same to any Third Party, without Ionis&#8217; prior written consent. For purposes of a Manufacturing Technology Transfer, the Parties together with Ionis&#8217; CMO (subject to the next sentence) will enter into a manufacturing technology transfer
                agreement, which will also provide for reasonable technical assistance and support by Ionis and Ionis&#8217; CMOs as reasonably requested by Otsuka to enable Otsuka or its Affiliates, or if agreed by Ionis, a Third Party manufacturer (other than
                Ionis&#8217; CMOs), to Manufacture the Licensed Products (a, &#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Technology Transfer Agreement</font>&#8221;). Ionis will use reasonable efforts to [***]. If Ionis agrees to transfer Ionis
                Manufacturing and Analytical Know-How to a Third Party manufacturer other than Ionis&#8217; CMOs, such transfer shall be carried out pursuant to a direct license between Ionis and such Third Party manufacturer. If Otsuka [***]. Otsuka will [***].
                Accordingly, Ionis may [***]. Otsuka will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">ARTICLE 8</div>
      <div style="text-align: center; font-weight: bold;">GOVERNANCE</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc007665630be4f2eb560e870fefa7555">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-weight: bold;">Executive Committee.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0327cda4ef0e4e0c938eabaa669d177d">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.1.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Formation and Purpose of the Executive Committee. Promptly, but not more than [</font>***<font style="font-weight: bold;">] after the Restatement Date, Ionis and Otsuka will establish an executive
                  committee (&#8220;Executive Committee&#8221;), which will have the responsibilities set forth in this </font><u>Section 8.1</u> (Executive Committee). The Executive Committee will dissolve upon the expiration of the Term.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">29</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
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      </div>
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          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.1.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Membership. The Executive Committee will be composed of an equal number of representatives from each Party who have the appropriate and direct knowledge and expertise and requisite decision-making
                  authority; </font><font style="font-weight: bold; font-style: italic;">provided</font><font style="font-weight: bold;"> that at least one representative from each Party will be an Executive Officer of such Party. Any such representative
                  who serves on the Executive Committee may also serve on one or more other committees under this Agreement.</font><font style="font-weight: bold; font-style: italic;">&#160;</font><font style="font-weight: bold;">Each Party may replace any of
                  its representatives on the Executive Committee and appoint a person to fill the vacancy arising from each such replacement. A Party that replaces a representative </font>will notify the other Party at least [***] prior to the next
                scheduled meeting of the Executive Committee. Ionis will designate one of its Executive Committee members as one of the co-chairpersons of the Executive Committee and Otsuka will designate one of its members as the other co-chairperson of
                the Executive Committee (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Executive Committee Co-Chairperson</font>&#8221;). The Executive Committee Co-Chairpersons or their designees, in collaboration with the Alliance Managers,
                will be responsible for calling meetings, preparing and circulating an agenda and related information in advance of each meeting, and preparing and issuing minutes of each meeting within [***] thereafter. Such minutes will not be finalized
                until the Executive Committee Co-Chairpersons or their designees have had [***] to review and confirm the accuracy of such minutes.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6b30cc0459974d44a16bd0f85399ea66">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.1.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Meetings</font>. The Executive Committee will hold meetings [***]. The Executive Committee may meet in person or by means of teleconference, Internet conference, video conference, or other similar
                communication method. Each Party will be responsible for all of its own costs and expenses of participating in any JSC meeting.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf5907a4d148e405e8646157db07d6fce">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.1.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Meeting Agendas</font>. Unless agreed otherwise by the Parties, the Parties will jointly prepare the agenda for each Executive Committee meeting, facilitated by the Alliance Managers working closely with
                the Executive Committee Co-Chairpersons and, as appropriate, other Executive Committee members and Subcommittee Co-Chairpersons, at least [***] in advance of each meeting of the Executive Committee, and each Party will provide the other
                Party with all relevant materials to be presented at each Executive Committee meeting at least [***] in advance of each meeting of the Executive Committee; <font style="font-style: italic;">provided</font> that under exigent circumstances
                requiring Executive Committee input, the agenda may be prepared or presentation materials may be provided within a shorter period of time in advance of a meeting, with the approval of the Executive Committee Co-Chairpersons. Either Party
                may propose that there not be a specific agenda for a particular meeting, so long as the other Party consents to the later addition or modification of agenda items or the absence of a specific agenda for such Executive Committee meeting.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9afd7222627d413e83cf2cc2fe35608c">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.1.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Specific Responsibilities of the Executive Committee</font>. The responsibilities of the Executive Committee will be to:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z48c71edd19f24c34ae607f19d9c89304">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>establish and delegate specifically defined duties to any Subcommittees, as described in <u>Section 8.3.1</u> (Formation; Authority);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc61a5e47f3924ff68ad13519cb997bcc">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>attempt to resolve any disputes or disagreements arising from matters within the jurisdiction of the Europe JSC, the Asia JSC, the PV Subcommittee or any other Subcommittee established by the Executive Committee; and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za51cc4d36f7147b2b1280773a6d179a0">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>perform such other functions as appropriate to further the purposes of this Agreement as determined by the Parties.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb72c990d17164d0da01603bc1c845d65">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Joint Steering Committees</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd8e91f8ce73a47cb8800f2d59babb01d">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.2.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Formation and Purposes of the Joint Steering Committees</font>. As of the Restatement Date, the Parties have established a Joint Steering Committee for the Europe Territory, which will have the
                responsibilities set forth in this <u>Section 8.2</u> (Joint Steering Committees) (&#8220;<font style="font-weight: bold; font-style: italic;">Europe JSC</font>&#8221;). Promptly, but not more than [***] after the Restatement Date, Ionis and Otsuka
                will establish a Joint Steering Committee for the Asia Territory, which will have the responsibilities set forth in this <u>Section 8.2</u> (Joint Steering Committees) (the &#8220;<font style="font-weight: bold; font-style: italic;">Asia JSC</font>,&#8221;




                and together with the Europe JSC, the &#8220;<font style="font-weight: bold; font-style: italic;">JSCs</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">30</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
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      </div>
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            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.2.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Membership</font>. As of the Restatement Date, the Europe JSC is, and each of the JSCs will be throughout the Term, composed of an equal number of representatives from each Party who have the appropriate
                and direct knowledge and expertise and requisite decision-making authority. Any such representative who serves on the JSCs may also serve on one or more other committees under this Agreement. Additional terms relating to the JSCs, including
                terms relating to JSC meetings and meeting agendas, are set forth in <u>Section 8.3.2</u> (Subcommittee Leadership and Meetings).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb615ed3ef42a422ca435fac6f8bf65f8">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.2.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Specific Responsibilities of the Europe JSC</font>. The Europe JSC will have the following responsibilities:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z565ed9b395004d65b6182ca63b5f09de">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>manage the overall strategic alignment between the Parties under this Agreement and maintain the relationship between the Parties;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z710702f389a142e08d5eb03ff0ae7c2f">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>oversee, review, monitor, and coordinate, and, where specified in this <u>Section 8.2.3</u> (Specific Responsibilities of the Europe JSC), approve the Parties&#8217; Development, Manufacturing, Medical Affairs, and Commercialization
                activities under this Agreement for the Licensed Products in the Territory (excluding the Asia Territory to the extent within the responsibilities of the Asia JSC);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6400edbfb46a4d3a97f2985c87272f18">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine whether to [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z07a24d1294f24d09b68f5004bfee8e43">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(d)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine (at a joint meeting with the Asia JSC) whether [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zca3456dee41b4034bf6b78324e65f132">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(e)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine whether [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z881ecceb639548d2a83b9036b34cd863">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(f)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine whether [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfc22bb15d0f84f18a03b551d26c63fbb">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(g)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss and determine whether [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8cdab4b25954432fbc8e7f0c4e9b3556">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(h)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine whether to approve any updates to the Shared Development Budget, as described in <u>Section 4.4.2(a)</u> (Shared Development Budget);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z86eb55da91ab4434b3b8c6db62d5788f">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(i)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine whether to approve [***] and the Shared Development Budget, as described in <u>Section 4.4.4(a)</u> (Shared Costs);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4769e2265e574675b43632298c915477">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(j)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>share information related to, and review and discuss activities and progress of each Party (A) in connection with the Development of Licensed Products in the Europe Territory and Ionis Territory and (B) under the Cross-Territory Clinical
                Development Plan, including through updates from each Party of the status of Development for the Licensed Products in each such Territory, as described in <u>Section 4.5</u> (Development Reports);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">31</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z84516e8295dd4714a6cccd41b5d85ece">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(k)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>share information related to, and review and discuss activities and progress under the Europe Territory-Specific Development Plan, and the Non-Clinical Europe HAE Development Plan, as described in <u>Section 4.5</u> (Development
                Reports);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zdf56bc350e154281aff0fae338f79d2f">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(l)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review and discuss any matters related to the Development of the Licensed Products applicable to the Europe Territory referred to the Europe JSC by either Party&#8217;s representatives, including matters related to the Development of the
                Licensed Products applicable to both the Europe Territory and the Asia Territory that are referred to a joint meeting of the Europe JSC and the Asia JSC by either Party&#8217;s representatives;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd877cc0a0bf14d52b33de783371728b8">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(m)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>discuss any concerns raised by either Party regarding any action that the other Party is taking or intends to take with respect to a Licensed Product that is [***], as described in <u>Section 5.8</u> (No Harmful Actions);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3ab2642ea9914609a5f03a128946e890">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(n)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>discuss [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb8ca6b6c15624f1891ae6ee62509948f">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(o)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine whether to approve [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z609fa4ea46474097a66a100c566e5073">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(p)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine whether to approve [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8a68ed8ff4a440d8bd8cf695401b1f57">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(q)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine whether to approve [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z23844e88525c4289b0b37b95b1975e5c">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(r)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss and determine whether to approve [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zbf8a585833364da794331b08d8281724">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(s)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review and discuss any matters related to the Commercialization of the Licensed Products applicable to the Europe Territory that are referred to the Europe JSC by either Party&#8217;s representatives, including matters related to the
                Commercialization of the Licensed Products applicable to both the Europe Territory and the Asia Territory that are referred to a joint meeting of the Europe JSC and the Asia JSC by either Party&#8217;s representatives;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0d5f5edfbb584754bbe2b18cd8ccf8c3">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(t)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>establish and delegate specifically defined duties to any Subcommittees, as described in <u>Section 8.3.1</u> (Formation; Authority);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfdf46592b20b4c699b0e89a30c45012b">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(u)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss and determine whether to approve [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3945eaf974fb456f96f80642a8aeb4cd">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(v)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>discuss the inclusion of Ionis&#8217; logo, name, and housemark on the packaging for the Licensed Products in the Europe Territory, as described in <u>Section 10.10.6</u> (Housemarks);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5eb5f3eebb5847e98ffc3e90fe4dcbe8">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(w)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>attempt to resolve any disputes or disagreements arising from matters within the jurisdiction of the Europe Regulatory Subcommittee or any other Subcommittee established by the Europe JSC; and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6d44a7ebda5340bdb1472b851983f967">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(x)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>perform such other functions as appropriate to further the purposes of this Agreement as determined by the Parties.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">32</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1e75a7d791934b759b958b6593374778">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.2.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Specific Responsibilities of the Asia JSC</font>. The Asia JSC will have the following responsibilities:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z877c089ec3484aac8981b72bfab96d8e">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>oversee, review, monitor, and coordinate, and, where specified in this <u>Section 8.2.4</u> (Specific Responsibilities of the Asia JSC), approve the Parties&#8217; Development, Manufacturing, Medical Affairs, and Commercialization activities
                under this Agreement for the Licensed Products in the Asia Territory;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zefa0a053bde243fa848a3d6a910677ca">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine whether to [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zba970f933bb944a2a655d08fd7799f3b">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine (at a joint meeting with the Europe JSC) whether [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z177e4d15ff9240febddbe429a2801031">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(d)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine whether [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z77f8c967ae76400baba7cc1b349c862d">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(e)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss and determine whether [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze2ec85f7f5e7446c96cbf2dd7bf10c1b">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(f)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>share information related to, and review and discuss activities and progress under the Asia Territory-Specific Development Plan and the Non-Clinical Asia HAE Development Plan, as described in <u>Section 4.5</u> (Development Reports);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z65662ad3e3f3441590baf9a07c6f956c">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(g)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review and discuss any matters related to the Development of the Licensed Products applicable to the Asia Territory that are referred to the Asia JSC by either Party&#8217;s representatives, including matters related to the Development of the
                Licensed Products applicable to both the Europe Territory and the Asia Territory that are referred to a joint meeting of the Europe JSC and the Asia JSC by either Party&#8217;s representatives;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5979450226684fb3a8fb244e5fa93470">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(h)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>discuss any concerns raised by either Party regarding any action that the other Party is taking or intends to take with respect to a Licensed Product that is [***], as described in <u>Section 5.8</u> (No Harmful Actions);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9ea876eec49445daa517d6b178ed0dd4">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(i)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss, and determine whether to [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z12b0e023229b47fc8932f23789b2a4ff">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(j)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss and determine whether to [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z74db5aadd5a14c61ae61e43895ea8e66">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(k)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review and discuss any matters related to the Commercialization of the Licensed Products applicable to the Asia Territory that are referred to the Asia JSC by either Party&#8217;s representatives, including matters related to the
                Commercialization of the Licensed Products applicable to both the Europe Territory and the Asia Territory that are referred to a joint meeting of the Europe JSC and the Asia JSC by either Party&#8217;s representatives;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za2cd194e072d41e9a77262b4d0b24583">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(l)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>establish and delegate specifically defined duties to any Subcommittees, as described in <u>Section 8.3.1</u> (Formation; Authority);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z83d034c5f3a14e47b5b137bd68f4d784">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(m)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>review, discuss and determine whether to [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6efb2307415f47e68b0456ec19d6f365">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(n)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>discuss the inclusion of Ionis&#8217; logo, name, and housemark on the packaging for the Licensed Products in the Asia Territory, as described in <u>Section 10.10.6</u> (Housemarks);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc17221a8177f4fb689ce628ede25e443">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(o)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>attempt to resolve any disputes or disagreements arising from matters within the jurisdiction of any Subcommittee established by the Asia JSC; and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z718b72e1585f48ffae972f2ace6cee77">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(p)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>perform such other functions as appropriate to further the purposes of this Agreement as determined by the Parties.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">33</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za25b493ad36b4490bf92e1fded3e05e5">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Subcommittees</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5f147e88b46e438eb670065a5b5467d8">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.3.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Formation; Authority</font>. In addition to the Europe Regulatory Subcommittee, the PV Subcommittee, and each JSC, the Executive Committee and the JSCs (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Establishing Committee</font>&#8221;) may establish and delegate specifically defined duties to operational committees or <font style="font-style: italic;">ad hoc</font> subcommittees, on an &#8220;as needed&#8221; basis to oversee
                particular projects or activities (any such operational committees and subcommittees, including the Europe Regulatory Subcommittee, the PV Subcommittee, and each JSC, a &#8220;<font style="font-weight: bold; font-style: italic;">Subcommittee</font>&#8221;).




                Both of the JSCs and the PV Subcommittee are Subcommittees of the Executive Committee and the Europe Regulatory Subcommittee is a Subcommittee of the Europe JSC. Any representative who serves on any Subcommittee under this Agreement may
                also serve on one or more other committees under this Agreement.<font style="font-style: italic;">&#160;</font>Subject to <u>Section 8.2</u> (Joint Steering Committees), each Subcommittee will be constituted and will operate as the applicable
                Establishing Committee determines. Each Subcommittee and its activities (other than the JSCs and their activities) will be subject to the oversight of, and will report to, the applicable Establishing Committee. Each Establishing Committee
                or its co-chairpersons, in each case as mutually agreed, may delegate to a Subcommittee any responsibilities of such Establishing Committee set forth in <u>Section 8.1</u> (Executive Committee) or <u>Section 8.2</u> (Joint Steering
                Committees), and, in such case, any agreement reached by unanimous Party Vote of the applicable Subcommittee with respect to such delegated responsibilities will be deemed to be approved by the applicable Establishing Committee (to the
                extent such approval is required hereunder). Each Establishing Committee or its co-chairpersons acting together may also reallocate any responsibility of a Subcommittee to any other Subcommittee. No Subcommittee&#8217;s authority may exceed that
                specified for the applicable Establishing Committee in this <u>Article 8</u> (Governance). Any disagreement between the representatives of the Parties on a Subcommittee will be referred to the applicable Establishing Committee for
                resolution in accordance with <u>Section 8.5</u> (Decision-Making).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0cc0a608e73d4119839c5f767600c155">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.3.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Subcommittee Leadership and Meetings</font>. Ionis will designate a co-chairperson of each Subcommittee and Otsuka will designate a co-chairperson of each Subcommittee, each of whom will be a Party&#8217;s
                representative who is a member of such Subcommittee (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Subcommittee</font><font style="font-style: italic;">&#160;</font><font style="font-weight: bold; font-style: italic;">Co-Chairperson</font>&#8221;).




                The Subcommittee Co-Chairpersons or their designees, in collaboration with the Alliance Managers, will be responsible for calling meetings, preparing and circulating an agenda in advance of each meeting, and preparing and issuing minutes of
                each meeting promptly thereafter; <font style="font-style: italic;">provided</font> that, as it relates to the JSC meetings, (a) the agenda will be prepared at least [***] in advance of such meeting, (b) each Party will provide the other
                Party with all relevant materials to be presented at such JSC meeting at least [***] in advance of such meeting, in each case, unless there are exigent circumstances requiring JSC input, in which case, the agenda may be prepared or
                presentation materials may be provided within a shorter period of time in advance of such JSC meeting, with the approval of the Subcommittee Co-Chairpersons of the applicable JSC, and (c) minutes of such JSC meeting will be issued within
                [***] thereafter. Such minutes will not be finalized until (i) as it relates to the JSC meetings, the Subcommittee Co-Chairpersons or their designees have had [***] to review and confirm the accuracy of such minutes, or (ii) as it relates
                to any Subcommittee meeting other than the JSC meetings, all Subcommittee members have had [***] to review and confirm the accuracy of such minutes. Each Party may replace its representatives and Subcommittee Co-Chairpersons on each such
                Subcommittee at any time upon written notice to the other Party; <font style="font-style: italic;">provided</font> that, if such replacement relates to a JSC, then such Party making such replacement will notify the other Party at least
                [***] prior to the next scheduled meeting of the applicable JSC. The Alliance Manager of each Party (or his or her designee) will attend each meeting of each Subcommittee as a non-voting participant. Each Subcommittee will hold meetings at
                such times as it elects to do so, and at such locations as the Parties may agree upon or by means of teleconference, Internet conference, video conference, or other similar communication method; <font style="font-style: italic;">provided</font>
                that, each JSC will meet no less frequently than quarterly prior to receipt of Regulatory Approval for the first Licensed Product in the Europe Territory or the Asia Territory, as applicable, and thereafter no less frequently than [***], in
                each case, unless otherwise agreed by the Parties. Each Party will be responsible for all of its own expenses of participating in any Subcommittee meeting.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">34</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z317f24b7ba444c828ad9e2c8e7c885b5">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Additional Participants</font>. Employees of a Party or any of its Affiliates involved in the Exploitation of the Licensed Products may attend meetings of the Executive Committee, a JSC, or any other
                Subcommittee as non-voting participants. In addition, with the prior consent of each Party, consultants, representatives, or advisors involved in the same activities and under written obligations of confidentiality and non-use applicable to
                the Confidential Information of each Party that are at least as stringent as those set forth in <u>Article 12</u> (Confidentiality) may attend meetings of the Executive Committee, a JSC or any other Subcommittee as non-voting observers.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc9ce06b29cd9479380129ead5ac288ba">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Decision-Making</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd8eb586d2003405a970f345b64cc400f">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.5.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">General Decision-Making Process</font>. Each Party&#8217;s representatives on the Executive Committee, each JSC, and each other Subcommittee will, collectively, have one vote (the &#8220;<font style="font-weight: bold; font-style: italic;">Party Vote</font>&#8221;) on all matters brought before such committee for a decision by consensus. The Executive Committee, each JSC, and each other Subcommittee will make decisions as to matters within its
                jurisdiction by unanimous Party Vote, which may be reflected in the minutes of the committee meeting or by an action by written consent signed by the Executive Committee Co-Chairpersons or the Subcommittee Co-Chairpersons, as applicable, or
                their designees identified in writing. Except as otherwise expressly set forth in this Agreement, the phrase &#8220;determine,&#8221; &#8220;designate,&#8221; &#8220;approve,&#8221; or &#8220;determine whether to approve&#8221; by the Executive Committee, either JSC or any other
                Subcommittee and similar phrases used in this Agreement will mean approval in accordance with this <u>Section 8.5</u> (Decision&#8209;Making) or <u>Section 8.6</u> (Resolution of Committee Disputes), including the escalation and tie&#8209;breaking
                provisions herein. For the avoidance of doubt, matters that are specified in <u>Section 8.2.3</u> (Specific Responsibilities of the Europe JSC) or <u>Section 8.2.4</u> (Specific Responsibilities of the Asia JSC) to be reviewed and
                discussed (as opposed to reviewed, discussed, and approved) do not require any agreement or decision by either Party and are not subject to the voting and decision-making procedures set forth in this <u>Section 8.5</u> (Decision&#8209;Making) or
                <u>Section 8.6</u> (Resolution of Committee Disputes).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf73b6a2a10e347ef95812103c155c8dd">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.5.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Decisions of the Subcommittees</font>. If any Subcommittee cannot reach unanimous agreement using good faith efforts on any matter within their respective scope of authority within [***] of the meeting at
                which such matter was discussed, then a Party may refer such matter to the applicable Establishing Committee for resolution in accordance with <u>Section 8.5.3</u> (Decisions of Establishing Committees).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">35</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z97040bb612c54578a54b1f2df46ea089">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.5.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Decisions of Establishing Committees</font>. If any Subcommittee established by a JSC is unable to reach a consensus decision on a matter within the scope of such Subcommittee&#8217;s authority in accordance
                with <u>Section 8.5.2</u> (Decisions of the Subcommittees), then, at either Party&#8217;s request, each Party will submit in writing its respective positions with respect to such unresolved matter to the applicable JSC and if such JSC, after the
                use of good faith efforts, including reasonable discussion and good faith consideration of each Party&#8217;s view on a particular matter, is unable to resolve such matter within a period of [***] after each Party submits in writing its
                respective position with respect to such matter, then either Party may refer such matter to the Executive Committee. If a JSC or other Subcommittee established by the Executive Committee is unable to reach a consensus decision on a matter
                within the scope of such JSC&#8217;s or other Subcommittee&#8217;s authority in accordance with <u>Section 8.5.2</u> (Decisions of the Subcommittees) or a JSC is unable to reach a consensus decision on a Subcommittee-related matter submitted to such
                JSC pursuant to the first sentence of this <u>Section 8.5.3</u> (Decisions of Establishing Committees), then, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z82d550df33af4e10a27ef717d68f572b">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.6</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Resolution of Committee Disputes</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5e9b0934b85843a78be4c74035f683dd">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.6.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Final Decision-Making Authority</font>. For any matter referred to the Executive Committee in accordance with <u>Section 8.5.3</u> (Decisions of Establishing Committees), if the Executive Committee is
                unable to reach a consensus decision on such matter, then, with respect to any matter set forth in clauses (b) and (c) of this <u>Section 8.6.1</u> (Final Decision-Making Authority), the applicable Executive Committee Co-Chairperson
                appointed by the Party with final-decision making authority over such matter will make a final decision on such matter in accordance with this <u>Section 8.6.1</u> (Final Decision-Making Authority) and subject to <u>Section 8.6.2</u>
                (Limitations on Decision Making). Any matter set forth in clause (a) of this <u>Section 8.6.1</u> (Final Decision-Making Authority) shall be subject to the mutual agreement of both Parties and, unless and until such mutual agreement is
                reached (by consensus decision of the applicable JSC or Executive Committee), the status quo will be maintained.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf6b761e4e7da4038be1dd0473be5cb8f">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">No Change; Status Quo</font>. Neither Party&#8217;s Executive Committee Co-Chairperson will have final decision-making authority with respect to the final resolution of any disagreement related to: (i) [***];
                (ii) [***]; (iii) [***]; (iv) [***]; (v) [***]; (vi) [***]; (vii) [***]; (viii)&#160; [***]; and (ix) [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z653b93e5d5874b1d8590afffffd9cbe6">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ionis Final Decision-Making Authority</font>. The Executive Committee Co-Chairperson for Ionis will have final decision-making authority over (i) [***], (ii) [***], (iii) [***], (iv) [***], (v) [***], and
                (vi) [***]. Notwithstanding the foregoing, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z179099fb340847bf84497de4bf67ebd3">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Final Decision-Making Authority</font>.<font style="font-weight: bold; font-style: italic;">&#160;</font>The Executive Committee Co-Chairperson for Otsuka will have final decision making authority over
                (i) [***], (ii) [***], (iii) [***], (iv) [***], (iv) [***], and (v) [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf737154896e045c799b91bc6fbdeb02a">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">8.6.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Limitations on Decision Makin</font>g. Notwithstanding anything to the contrary set forth in this Agreement, without the other Party&#8217;s prior written consent, no decision of the Executive Committee, either
                JSC, any other Subcommittee, or a Party&#8217;s Executive Committee Co-Chairperson (in the exercise of a Party&#8217;s decision&#8209;making authority on any such matters), in each case may, without the other Party&#8217;s prior written consent, (a) be likely to
                [***], (b) impose any requirements that the other Party take or decline to take any action that a Party reasonably believes would result in a violation of any Applicable Law, the requirements of any Regulatory Authority, or any agreement
                with any Third Party (including any Collaboration In-License) or the infringement or misappropriation of intellectual property rights of any Third Party, or (c) conflict with, amend, interpret, modify, or waive compliance under this
                Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">36</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z89cfd999f00245109bba7cb8ed5ed695">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.7</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Day-to-Day Responsibilities</font>. Each Party will: (a) be responsible for day-to-day implementation and conduct of the activities hereunder for which it has or is otherwise assigned responsibility under
                this Agreement, <font style="font-style: italic;">provided</font> that such implementation is consistent with the express terms of this Agreement or the decisions of the Executive Committee, either JSC, or any other Subcommittee, in each
                case, within the scope of its authority as provided herein; and (b) provide the other Party with information about material events related to the progress of such activities, as may be reasonably requested by the other Party from time to
                time.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0c9b0a6cdb534533a47db7852bad19fd">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.8</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Alliance Managers</font>. As of the Restatement Date, each of the Parties has appointed a representative of such Party to act as its alliance manager under this Agreement for the Europe Territory and,
                within [***] after the Restatement Date, each Party will appoint a representative to act as its alliance manager under this Agreement for the Asia Territory (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Alliance Manager</font>&#8221;).




                The role of the Alliance Managers is to act as a single point of contact between the Parties to ensure a successful relationship under this Agreement. All of the Alliance Managers will attend all Executive Committee meetings and joint
                meetings of the JSCs, the Alliance Managers for each Region shall attend the applicable JSC meetings, and the Alliance Managers or their respective designees will attend all other Subcommittee meetings and will support the Executive
                Committee Co-Chairpersons and any Subcommittee Co-Chairpersons in the discharge of their responsibilities. Alliance Managers will be non-voting participants in all Executive Committee and Subcommittee meetings, but an Alliance Manager may
                bring any matter to the attention of the Executive Committee or any Subcommittee if such Alliance Manager reasonably believes that such matter warrants such attention. Each Party may change its designated Alliance Manager(s) at any time
                upon written notice to the other Party. Any Alliance Manager may designate a substitute to temporarily perform the functions of that Alliance Manager by written notice to the other Party. Each Alliance Manager, with respect to each Region,
                or all Alliance Managers with respect to the Territory, will also: (a) be the point of first referral in all matters of conflict resolution; (b) provide a single point of communication for seeking consensus between the Parties regarding key
                strategy and plan issues; (c) identify and bring disputes to the attention of the JSCs or Executive Committee in a timely manner; (d) plan and coordinate cooperative efforts and internal and external communications; and (e) take
                responsibility for ensuring that governance activities, such as the conduct of required Executive Committee and any Subcommittee meetings and production of meeting minutes, occur as set forth in this Agreement, and that the relevant action
                items resulting from such meetings are appropriately carried out or otherwise addressed.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">ARTICLE 9</div>
      <div style="text-align: center; font-weight: bold;">PAYMENTS</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5cbd6e8ff1a24fa09e568d2fcc7cc929">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Upfront Payment</font>. The Parties acknowledge that, in connection with the execution of the Original Agreement, Otsuka paid to Ionis $65,000,000.&#160; Following the Restatement Date, within [***], Otsuka
                will pay to Ionis, by wire transfer of immediately available funds, a non-refundable, non-creditable upfront payment of $20,000,000 (the &#8220;<font style="font-weight: bold; font-style: italic;">Restatement Upfront Payment</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc3adaef788b74315872c6f4dd03cf72e">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Milestone Payments</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0be2123b9e3d4852bedc7c1757bce7ae">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">9.2.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Regulatory Milestones</font>. Subject to <u>Section 9.2.1(a)</u> (Europe Territory Regulatory Milestone Adjustment), after the first achievement of each regulatory milestone event set forth in Table
                9.2.1 below by Otsuka or its Affiliates or Sublicensees for the first Licensed Product, Otsuka will pay to Ionis the corresponding regulatory milestone payment set forth in Table 9.2.1 (the regulatory milestone events set forth in Table
                9.2.1, the &#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Milestone Events</font>&#8221; and the regulatory milestone payments set forth in Table 9.2.1, the &#8220;<font style="font-weight: bold; font-style: italic;">Regulatory
                  Milestone Payments</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">37</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
    </div>
    <div>
      <div>
        <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: rgb(0, 0, 0);">

            <tr>
              <td colspan="1" style="width: 1%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td colspan="3" style="vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">Table 9.2.1 &#8211; Regulatory Milestones</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 1%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td colspan="2" style="vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-style: italic; font-weight: bold;">Regulatory Milestone Event</div>
              </td>
              <td style="width: 30.68%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-style: italic; font-weight: bold;">Regulatory Milestone </div>
                <div style="text-align: center; font-style: italic; font-weight: bold;">Payment (in U.S. </div>
                <div style="text-align: center; font-style: italic; font-weight: bold;">Dollars)</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 1%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 2%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">1.&#160;&#160;&#160;</div>
              </td>
              <td style="width: 66%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">[***]</td>
              <td style="width: 30.68%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 1%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 2%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">2.&#160;&#160; <br>
                </div>
              </td>
              <td style="width: 66%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">[***]</td>
              <td style="width: 30.68%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 1%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 2%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">3.&#160;&#160;&#160;</div>
              </td>
              <td style="width: 66%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">[***]</td>
              <td style="width: 30.68%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 1%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 2%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">4.&#160;&#160; <br>
                </div>
              </td>
              <td style="width: 66%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">[***]</td>
              <td style="width: 30.68%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">(a) $[***]</div>
                <div style="text-align: center;">or</div>
                <div style="text-align: center;">(b) $[***]</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 1%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 2%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">5. &#160;&#160;</div>
              </td>
              <td style="width: 66%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">[***]</td>
              <td style="width: 30.68%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1a91b2fc6ce44f238f49f50fa586ee64">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Europe Territory Regulatory Milestone Adjustment</font>. If any [***], then the Regulatory Milestone Payments for the Europe Territory [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z29d1a77f2d3c4d30a7881945ba94a3f5">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Notice and Payment</font>. Otsuka will notify Ionis in writing of the achievement of each Regulatory Milestone Event within [***] after achievement of such Regulatory Milestone Event by Otsuka or its
                Affiliates or within [***] after Otsuka&#8217;s receipt of notification of such achievement by its Sublicensees. However, in no event will a failure or delay by Otsuka<font style="font-weight: bold; font-style: italic;">&#160;</font>to deliver such
                notice of achievement of a Regulatory Milestone Event relieve Otsuka of its obligation to pay Ionis the corresponding Regulatory Milestone Payment for achievement of such Regulatory Milestone Event. Following receipt of such notice, Ionis
                will send Otsuka an invoice (and, if there has been any change to a Payment Form previously submitted, or if a previously submitted Payment Form has expired, then an updated Payment Form) for the applicable Regulatory Milestone Payment, and
                Otsuka shall pay such Regulatory Milestone Payment within [***] after receipt of such invoice (and Payment Forms, if applicable). Each Regulatory Milestone Payment<font style="font-weight: bold;">&#160;</font>is payable only once, regardless of
                the number of times the corresponding Regulatory Milestone Event is achieved. If Otsuka or its Affiliates or Sublicensees achieve all of the Regulatory Milestone Events, then the Regulatory Milestone Payments payable by Otsuka under this <u>Section




                  9.2.1</u> (Regulatory Milestones) will not exceed $[***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc70ce90b24c2413980e220caffec9196">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">9.2.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Sales Milestones</font>. After each sales milestone event set forth in Table 9.2.2 below is achieved by Otsuka or its Affiliates or Sublicensees for the Licensed Products in the Europe Territory or the
                Asia Territory, as applicable, Otsuka will pay to Ionis the corresponding sales milestone payment, as set forth below (the sales milestone events set forth in Table 9.2.2, the &#8220;<font style="font-weight: bold; font-style: italic;">Sales
                  Milestone Events</font>&#8221; and the sales milestone payments set forth in Table 9.2.2, the &#8220;<font style="font-weight: bold; font-style: italic;">Sales Milestone Payments</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">38</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
    </div>
    <div>
      <div>
        <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: rgb(0, 0, 0);">

            <tr>
              <td colspan="1" style="width: 1%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td colspan="3" style="vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">Table 9.2.1 &#8211; Regulatory Milestones</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 1%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td colspan="2" style="vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-style: italic; font-weight: bold;">Regulatory Milestone Event</div>
              </td>
              <td style="width: 30.68%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-style: italic; font-weight: bold;">Regulatory Milestone </div>
                <div style="text-align: center; font-style: italic; font-weight: bold;">Payment (in U.S. </div>
                <div style="text-align: center; font-style: italic; font-weight: bold;">Dollars)</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 1%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 2%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">1.&#160;&#160;&#160;</div>
              </td>
              <td style="width: 66%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">[***]</td>
              <td style="width: 30.68%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 1%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 2%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">2.&#160;&#160; <br>
                </div>
              </td>
              <td style="width: 66%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">[***]</td>
              <td style="width: 30.68%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 1%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 2%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">3.&#160;&#160;&#160;</div>
              </td>
              <td style="width: 66%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">[***]</td>
              <td style="width: 30.68%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 1%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 2%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">4.&#160;&#160; <br>
                </div>
              </td>
              <td style="width: 66%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">[***]</td>
              <td style="width: 30.68%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">(a) $[***]</div>
                <div style="text-align: center;">or</div>
                <div style="text-align: center;">(b) $[***]</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 1%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 2%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">5. &#160;&#160;</div>
              </td>
              <td style="width: 66%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">[***]</td>
              <td style="width: 30.68%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z820063fe1b9a43dfb1da3ea7641f9521">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Notice and Payment</font>. Otsuka will notify Ionis in writing of the achievement of each Sales Milestone Event no later than (i) [***] or (ii) [***]. However, in no event will a failure or delay by
                Otsuka<font style="font-weight: bold; font-style: italic;">&#160;</font>to deliver such notice of achievement of a Sales Milestone Event relieve Otsuka of its obligation to pay Ionis the corresponding Sales Milestone Payment for achievement of
                such Sale Milestone Event. Following receipt of such notice, Ionis will send Otsuka an invoice (and, if there has been any change to a Payment Form previously submitted, or if a previously submitted Payment Form has expired, then an updated
                Payment Form) for the applicable Sales Milestone Payment, and Otsuka shall pay such Sales Milestone Payment within [***] after receipt of such invoice (and Payment Forms, if applicable). If more than one of the Sales Milestone Events is
                achieved for the first time in a given Calendar Quarter during the Term, then Otsuka will pay to Ionis a separate Sales Milestone Payment with respect to each such Sales Milestone Event. Each Sales Milestone Payment<font style="font-weight: bold;">&#160;</font>is payable only once, regardless of the number of times the corresponding Sales Milestone Event is achieved. If Otsuka or its Affiliates or Sublicensees achieve all of the Sales Milestone Events, then the Sales Milestone
                Payments payable by Otsuka under this <u>Section 9.2.2</u> (Sales Milestones) will not exceed $[***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb15182e7c05a4426b7be9c1f9af928e5">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Royalties</font><font style="color: rgb(0, 0, 0);">.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf6944337ba334cc3b35b059f929cdb5f">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">9.3.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Royalty Payments During the Initial Royalty Term</font>. Subject to the provisions of <u>Section 9.3.2</u> (Royalty Reductions), Otsuka will pay to Ionis royalties based on the Net Sales of a Licensed
                Product by Otsuka and its Affiliates and Sublicensees in the Otsuka Territory at the rates set forth in Table 9.3.1 below (the &#8220;<font style="font-weight: bold; font-style: italic;">Initial Royalties</font>&#8221;), on a Licensed
                Product-by-Licensed Product and country-by-country basis, commencing on the first sale of such Licensed Product that results in Net Sales of such Licensed Product in such country and ending on the latest to occur of (a) the [***]
                anniversary of the First Commercial Sale of such Licensed Product in such country, (b) the expiration of the last Valid Claim in the [***] that Cover such Licensed Product in such country [***], and (c) loss of Regulatory Exclusivity of
                such Licensed Product in such country (the &#8220;<font style="font-weight: bold; font-style: italic;">Initial Royalty Term</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">39</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
    </div>
    <div>
      <div>
        <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: rgb(0, 0, 0);">

            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td colspan="2" style="vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">Table 9.3.1&#8211; Royalty Rates for the Licensed Products</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 84.2%; vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-style: italic; font-weight: bold;">Calendar Year Net Sales of all Licensed Products in the Europe Territory or the Applicable Country or Jurisdiction in the Asia Territory</div>
              </td>
              <td style="width: 14.58%; vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-style: italic; font-weight: bold;">Royalty Rate</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td colspan="2" style="vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="font-style: italic; font-weight: bold;">Europe Territory</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 84.2%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in the Europe Territory that is [***]</div>
              </td>
              <td style="width: 14.58%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 84.2%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in the Europe Territory that is greater than [***]</div>
              </td>
              <td style="width: 14.58%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 84.2%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in the Europe Territory that is [***]</div>
              </td>
              <td style="width: 14.58%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td colspan="2" style="vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div><font style="font-weight: bold; font-style: italic;">[</font>***<font style="font-weight: bold; font-style: italic;">]</font></div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 84.2%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in [***] that is [***]</div>
              </td>
              <td style="width: 14.58%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 84.2%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in [***] that is [***]</div>
              </td>
              <td style="width: 14.58%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 84.2%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in [***] that is [***]</div>
              </td>
              <td style="width: 14.58%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 84.2%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in [***] that is [***]</div>
              </td>
              <td style="width: 14.58%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td colspan="2" style="vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div><font style="font-weight: bold; font-style: italic;">[</font>***<font style="font-weight: bold; font-style: italic;">]</font></div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 84.2%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in [***] that is [***]</div>
              </td>
              <td style="width: 14.58%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 84.2%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in [***] that is [***]</div>
              </td>
              <td style="width: 14.58%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 84.2%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in [***] that is [***]</div>
              </td>
              <td style="width: 14.58%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 84.2%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in [***] that is [***]</div>
              </td>
              <td style="width: 14.58%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td colspan="1" style="width: 0.97%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td style="width: 84.2%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in [***] that is [***]</div>
              </td>
              <td style="width: 14.58%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 36pt;">By way of example only, if Otsuka receives [***] in Net Sales of all Licensed Products during a given Calendar Year in the Europe Territory, then Otsuka would owe Ionis a royalty of [***] (as
        converted into U.S. Dollars in accordance with <u>Section 9.8</u> (Method of Payment; Exchange Rate)).</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze4293b72a4d4462c85f8eaf748d1ebf7">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">9.3.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Royalty Reductions</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z80a3f43162a34889817b6b9b1bc764b1">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Generic Approval</font>. On a country-by-country and Licensed Product-by-Licensed Product basis, if at any time during the Initial Royalty Term a Generic Product receives Regulatory Approval in a country
                in the Otsuka Territory, then, subject to <u>Section 9.3.2(e)</u> (Royalty Reductions Floor), the royalty rates set forth in Table 9.3.1 will be reduced by [***] for such Licensed Product in such country.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8e18447965ed402b83fd3aa7db28acaf">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Third Party Payments</font>. Subject to <u>Section </u><u>9.3.2(e)</u> (Royalty Reductions Floor), Otsuka may credit [***] of [***] in a country in the Otsuka Territory in a Calendar Quarter during the
                Royalty Term against the Royalties due and payable by Otsuka to Ionis on the Net Sales for such Licensed Product in such country in such Calendar Quarter; <font style="font-style: italic;">provided </font>that<font style="font-style: italic;">&#160;</font>the terms of this <u>Section </u><u>9.3.2(b)</u> (Third Party Payments) will not apply to any license agreement entered into without Ionis&#8217; prior written consent in violation of the terms of <u>Section 10.5.3</u>
                (Settlement). For clarity, Otsuka will not have the right to offset any Third Party Payments arising out of, or allocable to, the Manufacture of a Licensed Product.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">40</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z23245c09b6844e76a254a7d6f8af726f">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">[</font>***<font style="font-weight: bold;">]</font>. Subject to <u>Section 9.3.2(e)</u> (Royalty Reductions Floor), on a Licensed Product-by-Licensed Product and country-by-country basis, if during any
                Calendar Quarter during the Initial Royalty Term for such Licensed Product in such country, (i) [***], and (ii) [***], then, commencing [***];<font style="font-style: italic;"> provided </font>that, if [***], then [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z839ef7a3522f4558bc4564de32efbe97">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(d)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">[</font>***<font style="font-weight: bold;">]</font>. Subject to <u>Section 9.3.2(e)</u> (Royalty Reductions Floor), on a Licensed Product-by-Licensed Product and country-by-country basis, during the
                Initial Royalty Term for such Licensed Product in such country, if, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1983a1cb614845088ea590ad75bd8bf7">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(e)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Royalty Reductions Floor</font>. In no event will the Royalties due to Ionis for a Licensed Product in a country in the Otsuka Territory [***] set forth in this <u>Section </u><u>9.3.2</u> (Royalty
                Reductions). Notwithstanding the foregoing, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze23e43d51420420e81a17d0064a4a757">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">9.3.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Reduced Royalty Term</font>. On a Licensed Product-by-Licensed Product, country-by-country and Region-by-Region basis in the Otsuka Territory, following expiration of the Initial Royalty Term for a
                Licensed Product in a given country in a Region, Otsuka will pay Ionis a [***] royalty on the Net Sales of such Licensed Product by Otsuka and its Affiliates and Sublicensees in such country (the &#8220;<font style="font-weight: bold; font-style: italic;">Reduced Royalties</font>&#8221; and together with the Initial Royalties, the &#8220;<font style="font-weight: bold; font-style: italic;">Royalties</font>&#8221;) until the later of (a) [***], and (b) [***] (the &#8220;<font style="font-weight: bold; font-style: italic;">Reduced Royalty Term</font>&#8221; and together with the Initial Royalty Term, the &#8220;<font style="font-weight: bold; font-style: italic;">Royalty Term</font>&#8221;). For clarity, on a Licensed Product-by-Licensed Product and
                country-by-country basis, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb6f7fcc7d532456db44da657c0703de1">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">9.3.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Royalty Payments and Reports</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z12866211a6834fdbb92e536733ab0c3e">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">[</font>***<font style="font-weight: bold;">]</font>. Commencing with the Calendar Quarter during which the first sale of a Licensed Product is made that results in Net Sales anywhere in the Otsuka
                Territory, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1f500f33b4cf49359caa9f3449b38d26">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Royalty Report</font>. Commencing with the Calendar Quarter during which the first sale of a Licensed Product is made that results in Net Sales anywhere in the Otsuka Territory, within [***] after the end
                of each Calendar Quarter, Otsuka will provide to Ionis a written report (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Royalty Report</font>&#8221;) setting forth in reasonable detail: (i) the gross sales of the Licensed Products
                sold by Otsuka or its Affiliate or Sublicensee in each of the Europe Territory, [***] in such Calendar Quarter; (ii) the aggregate Net Sales of the Licensed Products sold by Otsuka or its Affiliates or Sublicensees in each of the Europe
                Territory, [***] in such Calendar Quarter; (iii) all deductions and reductions used to determine the Net Sales of the Licensed Products for such Calendar Quarter or the Royalties payable with respect to the Licensed Products for such
                Calendar Quarter, including any reduction pursuant to <u>Section 9.3.2</u> (Royalty Reductions) (if applicable); (iv) the exchange rates used to calculate the Royalties payable in U.S. Dollars; (v) any withholding taxes required to be made
                from such Royalties; and (vi) the quantity and description of the Licensed Products sold by Otsuka or its Affiliate or Sublicensee in each of the Europe Territory, [***] during such Calendar Quarter comprising such Net Sales. The Parties
                will seek to resolve any questions or issues related to a Royalty Report within [***] following receipt by Ionis of each Royalty Report.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zcfd69fdd0930443992b0424818e6f7bd">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Royalty Payments</font>. The information contained in each Royalty Report will be considered the Confidential Information of Otsuka. Following receipt of each Royalty Report, Ionis will [***] and, [***],
                Otsuka will pay the Royalties due hereunder for the Calendar Quarter covered by the applicable Royalty Report.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">41</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za498f30d12ec4ffc83bfd057008fd837">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Other Amounts Payable</font>. With respect to any amounts owed under this Agreement by one Party to the other for which no other invoicing and payment procedure is specified hereunder, within [***] after
                the end of each Calendar Quarter, each Party will provide an invoice, together with reasonable supporting documentation, to the other Party for such amounts owed in respect of such Calendar Quarter. The owing Party will pay any undisputed
                invoiced amounts within [***] after the date of the invoice, and any disputed amounts owed by a Party will be paid within [***] following resolution of the dispute.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z24d7d59ec15047388a41f98af37e8440">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Financial Records and Audits</font>. Each Party will, and will require its Sublicensees and Subcontractors to, maintain complete and accurate records in accordance with such Party&#8217;s Accounting Standards
                in sufficient detail to permit the other Party to confirm the accuracy of any amounts payable under this Agreement for at least the preceding [***] (<font style="font-style: italic;">provided</font> that, with respect to Internal Costs,
                such records may be based on estimates as long as the method of calculating such estimates is consistently applied),<font style="font-weight: bold; font-style: italic;">&#160;</font>including (as applicable) any External Costs incurred in
                connection with the performance of the Asia-Specific Non-Clinical HAE Development Activities, Eligible Cross-Territory Development Costs, Milestone Payments, Royalties, and sales of the Licensed Products (including all calculations of Net
                Sales). Upon reasonable prior notice, each Party agrees to permit such records to be open during regular business hours for examination by an independent certified public accountant selected by the auditing Party and reasonably acceptable
                to the audited Party for the sole purpose of verifying the accuracy of the financial reports furnished by the audited Party pursuant to this Agreement or of any payments made, or required to be made, by the audited Party pursuant to this
                Agreement; <font style="font-style: italic;">provided </font>that<font style="font-style: italic;">&#160;</font>such independent accounting firm is subject to written obligations of confidentiality and non-use applicable to each Party&#8217;s
                Confidential Information that are at least as stringent as those set forth in <u>Article 12</u> (Confidentiality). Such audit will not be (a) performed more frequently than [***], or (b) repeated for any Calendar Year or with respect to
                the same set of records (in each case, except for cause). Such auditor will not disclose the audited Party&#8217;s Confidential Information to the auditing Party or to any Third Party, except to the extent such disclosure is necessary to verify
                the accuracy of the financial reports furnished by the audited Party or the amount of payments by the audited Party under this Agreement. The audited Party will pay any amounts shown to be owed to the auditing Party but unpaid within [***]
                after the accountant&#8217;s report, <font style="font-style: italic;">plus</font> interest (as set forth in <u>Section 9.11</u> (Late Payments; Disputed Payments)) from the original due date solely if the audited Party is responsible for the
                discrepancy. If such examination of records reveals any overpayment by Ionis, then Otsuka will reimburse Ionis for the amount overpaid within [***] after the accountant&#8217;s report, <font style="font-style: italic;">plus</font> interest (as
                set forth in <u>Section 9.11</u> (Late Payments; Disputed Payments)) from the original due date [***]. If such examination of records reveals any overpayment by Otsuka, then [***]. The auditing Party will bear the full cost of such audit
                unless such audit reveals an underpayment by the audited Party of more than [***] of the amount actually due for the time period being audited, in which case the audited Party will reimburse the auditing Party for the reasonable audit fees
                for such examination.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfeef888eb5e043ee89c997165458cea7">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.6</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">No Refunds</font>. Except as expressly provided herein, all payments under this Agreement will be irrevocable, non-refundable, and non-creditable.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z18a6496fbb5e4708b6591ca0c214b466">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.7</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Accounting Standards</font>. If a Party changes its general accounting principles from its then-current Accounting Standard (<font style="font-style: italic;">e.g.</font>, from GAAP to IFRS) at any time
                during the Term, then at least [***] prior to adopting such change in principles, such Party will provide written notice to the other Party of such change. A Party may not change its general accounting principles to any accounting standard
                other than GAAP or IFRS without the prior written approval of the other Party.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">42</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z76b4a3e251f047cda06759b5be432981">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.8</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Method of Payment; Exchange Rate</font>. All amounts to be paid pursuant to this Agreement will be made in U.S. Dollars and will be paid by wire transfer in immediately available funds to a bank account
                designated by the receiving Party. The rate of exchange to be used in computing the amount of currency equivalent in U.S. Dollars owed to a Party under this Agreement will be the Selling Party&#8217;s then-current standard exchange rate
                methodology employed for the translation of foreign currency sales into U.S. Dollars in accordance with its Accounting Standards and consistently applied during the period.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4d68517f61244171ad388624276f2be4">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.9</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Blocked Payments</font>. If by reason of Applicable Law in any country or jurisdiction, it becomes impossible or illegal for a Party to transfer, or have transferred on its behalf, payments owed the other
                Party hereunder, then such Party will promptly notify the other Party of the conditions preventing such transfer and use reasonable efforts to deposit such payments in U.S. Dollars. If, after using reasonable efforts, such Party is not able
                to deposit such payments in U.S. Dollars, then such payments will be deposited in local currency in the relevant country to the credit of the other Party in a recognized banking institution designated by the other Party or, if none is
                designated by the other Party within [***], in a recognized banking institution selected by the transferring Party, as the case may be, and identified in a written notice given to the other Party<u>.</u></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z611d99758d954def9fa2b0648651f9a0">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.10</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Taxes</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z08c30c4464cb4c1693c785f53c8b22c0">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">9.10.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Taxes on Income</font>. Each Party will be solely responsible for the payment of any and all income Taxes levied on account of all payments it receives under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z65bbdad1c91d4eb49e8fa4b4af00b633">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">9.10.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Withholding Tax</font>. Any and all payments made pursuant to this Agreement will be paid without deduction or withholding for any Taxes, except as required by Applicable Law. To the extent a Party is
                required by Applicable Law to deduct or withhold Taxes on any payment to the other Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Withheld Amount</font>&#8221;), such Party will remit such Withheld Amount to the proper
                Governmental Authority in a timely manner and promptly transmit to the other Party an official Tax certificate or other evidence of any withholding sufficient to enable the other Party to claim available credits for such Withheld Amount.
                The withholding Party will have the right to deduct such Withheld Amount from payment due to the other Party. For the avoidance of doubt, to the extent such Withheld Amount is so withheld and remitted in accordance with this <u>Section
                  9.10.2</u> (Withholding Tax), such Withheld Amount will be treated for all purposes of this Agreement as having been paid to the other Party.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z62b6b665efec42358349d6f5dbe61bbd">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">9.10.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Tax Cooperation</font>. The Parties agree to cooperate with one another in accordance with Applicable Law and use reasonable efforts to [***] in respect of payments made by each Party to the other Party
                under this Agreement. Without limiting the generality of the foregoing, each Party will provide the other with any Tax forms and other information that may be reasonably necessary to [***] based on an applicable treaty or otherwise,
                including a properly completed Internal Revenue Service (&#8220;<font style="font-weight: bold; font-style: italic;">IRS</font>&#8221;) Form W-9 or appropriate IRS Form W-8, as applicable, before a payment is made. If any Tax form or other information
                a Party previously delivered expires or becomes obsolete or inaccurate in any respect, then such Party will provide the other Party with an updated version of such form or certification or promptly notify the other Party in writing of its
                legal inability to do so. Each Party will provide the other Party with reasonable assistance to enable the recovery, as permitted by Applicable Law, of withholding Taxes or similar obligations resulting from payments made under this
                Agreement, such recovery to be for the benefit of the Party bearing such withholding Tax.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">43</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0b5f717427f94f25bb4d73a40598c1a0">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">9.10.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Changes in Domicile</font>. Notwithstanding any provision to the contrary in this Agreement, including <u>Section 9.10.2</u> (Withholding Tax), if as a result of a Party assigning, transferring, or
                conveying rights under this Agreement to an Affiliate or changing its domicile, additional Taxes become due that would not otherwise have been due hereunder with respect to payments under this Agreement, then such Party will be responsible
                for all such additional withholding Taxes.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z30879abe3c17415bb217fe885bbae752">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.11</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Late Payments; Disputed Payments</font>. Any undisputed payments or portions thereof due hereunder that are not paid on or before the date such payments are due under this Agreement will bear interest
                from the due date until the date of payment at a per-annum rate equal to the lesser of: (a) [***] percentage points above the prime rate as published by <font style="font-style: italic;">The Wall Street Journal </font>or any successor
                thereto; or (b) the maximum rate permitted by Applicable Law. If a Party disputes an invoice or other payment obligation under this Agreement, then such Party will timely pay the undisputed amount of the invoice or other payment obligation,
                and the Parties will resolve such dispute in accordance with <u>Article 15</u> (Dispute Resolution; Governing Law).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">ARTICLE 10</div>
      <div style="text-align: center; font-weight: bold;">INTELLECTUAL PROPERTY</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z34394bc80d8c4ec2a8b380b898a2c698">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Inventions</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9015a397953649bc8bd28845d0f7d691">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.1.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ownership of Background Intellectual Property</font>. As between the Parties, and subject to the licenses granted under this Agreement, each Party retains all rights, title, and interests in and to all
                Patent Rights and Know-How that such Party owns or Controls as of the Original Effective Date or that it develops or otherwise acquires after the Original Effective Date outside the performance of the activities under the Original Agreement
                during the Original Agreement Term or under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf77d1c182c72428f9aece854b411d338">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.1.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ownership of Arising Intellectual Property</font>. As between the Parties, ownership of all Collaboration Know-How will be as follows:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zdef7d88d4ded4476ae721f34d901e0b0">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis will be the sole owner of any (i) Collaboration Know-How that is developed or invented solely by Representatives of Ionis or its Affiliates or its or their licensees (other than Otsuka), Sublicensees, or Subcontractors, or any
                Persons contractually required to assign or license such Collaboration Know-How to Ionis or any Affiliate of Ionis (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Know-How</font>&#8221;), and (ii) Patent Rights that
                Cover the Ionis Collaboration Know-How (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Patent Rights</font>&#8221;), and will retain all of its rights thereto, subject to any rights or licenses expressly granted by
                Ionis to Otsuka under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zdc71dd2fedac4a46b5567f1e3bd1b47c">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Otsuka will be the sole owner of any (i) Collaboration Know-How that is developed or invented solely by Representatives of Otsuka or its Affiliates or its or their licensees (other than Ionis), Sublicensees, or Subcontractors, or any
                Persons contractually required to assign or license such Collaboration Know-How to Otsuka or any Affiliate of Otsuka (&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Collaboration Know-How</font>&#8221;), and (ii) Patent Rights that
                Cover the Otsuka Collaboration Know-How (&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Collaboration Patent Rights</font>&#8221;), and will retain all of its rights thereto, subject to any rights or licenses expressly granted by
                Otsuka to Ionis under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z646cb7ff6dcc4da1a7e037ed1abe9cf9">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Each Party will own an equal, undivided share of all Joint Collaboration Technology.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">44</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zce75e55e92d44abf87bdd9f7aa29763c">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.1.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Disclosure; Inventorship</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3060213ca2e143e7a22502829501fb41">

          <tr>
            <td style="width: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-size: 12pt;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Invention Disclosure</font>. Each Party will promptly disclose to the other Party all Inventions within the Collaboration Know-How developed or invented during the Original Agreement Term or during the
                Term by or on behalf of such Party, in each case, as soon as practicable prior to an intended public disclosure of such Invention and prior to the filing of a patent application thereon. Each Party will also promptly respond to reasonable
                requests from the other Party for additional information relating thereto.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd2fe1c9d4f98436dbe770b7af515ce31">

          <tr>
            <td style="width: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-size: 12pt;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Inventions by a Party</font>. Inventorship for Inventions and discoveries (including Know-How) first invented or developed during the course of the performance of activities under the Original Agreement
                and this Agreement will be determined in accordance with United States Patent Laws for determining inventorship.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z14a56b59610a4f5db21434258d658800">

          <tr>
            <td style="width: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-size: 12pt;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Joint Research Agreement under the Leahy-Smith America Invents Act</font>. If a Party intends to invoke its rights under 35 U.S.C. &#167; 102(c) of the Leahy-Smith America Invents Act, then it will notify the
                other Party and neither Party will make an election under such provision when exercising its rights under this <u>Article 10</u> (Intellectual Property) without the prior written consent of the other Party (such consent not to be
                unreasonably withheld, conditioned, or delayed), and the Parties will use reasonable efforts to cooperate and coordinate their activities with respect to any submissions, filings or other activities in support thereof. The Parties
                acknowledge and agree that the Original Agreement and this Agreement is a &#8220;<font style="font-style: italic;">joint research agreement</font>&#8221; as defined in 35 U.S.C. &#167; 100(h).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zbb0b67ac86664245bc85e5a861736a4a">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.1.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Practice Under and Other Use of Joint Collaboration Technology</font>. Subject to the rights granted under and the restrictions set forth in this Agreement (including the licenses granted under <u>Article




                  2</u> (Licenses)), each Party will be entitled to the free use and enjoyment of all Joint Collaboration Technology and neither Party will have any obligation to account to the other Party for profits, or to obtain any approval of the
                other Party to license, assign, or otherwise exploit any Joint Collaboration Technology by reason of joint ownership thereof. Each Party hereby waives any right it may have under the Applicable Law of any jurisdiction to require any such
                approval or accounting. To the extent any further consent is required to enable a Party to so license or exploit its interest in the Joint Collaboration Technology, the other Party will grant consent promptly upon request. Without
                limitation, each Party will cooperate with the other Party if the Parties determine to apply for U.S. or foreign patent protection for any Joint Collaboration Technology and will obtain the cooperation of the individual inventors of any
                such Joint Collaboration Technology.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zdb285db6345041f8b115aa67fe717589">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.1.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Representative Assignment</font>. Each Party and its Affiliates will, and will cause its licensees, Sublicensees and Subcontractors to, enter into an agreement or employment policy with each of its
                Representatives performing activities related to Development, Manufacture, or Commercialization of a Licensed Product that (a) compels prompt disclosure to such Party (or its Affiliate, licensee, Sublicensee or Subcontractor, as applicable)
                of all Collaboration Know-How and Collaboration Patent Rights discovered, developed, invented, or filed by such Representative during any performance of such Development, Manufacture or Commercialization activities; and (b) automatically
                assigns to such Party (or its Affiliate, licensee, Sublicensee or Subcontractor, as applicable) all rights, title, and interests in and to all Collaboration Know-How and Collaboration Patent Rights, and requires each Representative to
                execute all documents and take such other actions as may be necessary to effectuate such assignment (or, if such assignment is not feasible, provides for such Party&#8217;s (or its Affiliate&#8217;s, licensee&#8217;s, Sublicensee&#8217;s or Subcontractor&#8217;s, as
                applicable) joint ownership of, or an irrevocable, royalty-free license to such Party (or its Affiliate, licensee, Sublicensee or Subcontractor, as applicable) under, all Collaboration Know-How and Collaboration Patent Rights, with the
                right to sublicense to the other Party as contemplated in this Agreement), <font style="font-style: italic;">provided</font> that the foregoing will not apply with respect to improvements to background technology of a Subcontractor.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">45</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z18e8b9ee8c894d1f87063a70a295efcb">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Patent Prosecution</font><font style="color: rgb(0, 0, 0);">.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z71210330fbff4c33a19391b82c7873f4">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.2.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ionis Patent Rights and Joint Collaboration Patent Rights</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc8fd7bbd48d24af695f3db65721d8d4f">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Right to Prosecute</font>. As between the Parties, Ionis will have the (i) first right, in its sole discretion, to control the Patent Prosecution of all Ionis Product-Specific Patents in the Otsuka
                Territory and all Joint Collaboration Patent Rights worldwide, and (ii) sole right, in its sole discretion, to control the Patent Prosecution of all (A) Ionis Product-Specific Patents in the Ionis Territory, and (B) Ionis Core Technology
                Patents and Ionis Manufacturing and Analytical Patents, in each case, worldwide (collectively, ((i) and (ii)), the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Prosecuted Patent Rights</font>&#8221;). Upon Ionis&#8217; request, Otsuka
                will obtain any necessary assignment documents for Ionis with respect to the Patent Prosecution of Ionis Prosecuted Patent Rights, will render all signatures that will be necessary for such patent filings, and will assist Ionis in all other
                reasonable ways that are necessary for the issuance of Ionis Prosecuted Patent Rights as well as for the Patent Prosecution of Ionis Prosecuted Patent Rights, and Ionis will reimburse Otsuka&#8217;s reasonable External Costs incurred in
                connection therewith. Ionis will be responsible for [***] of the costs and expenses incurred with respect to the Patent Prosecution of all Ionis Product-Specific Patents, Ionis Core Technology Patents and Ionis Manufacturing and Analytical
                Patents throughout the world and for [***] of the costs and expenses incurred with respect to the Patent Prosecution of Joint Collaboration Patent Rights in the Ionis Territory. Otsuka will be responsible for [***] of the reasonable
                out-of-pocket costs incurred by or on behalf of Ionis with respect to the Patent Prosecution of the Joint Collaboration Patent Rights in the Otsuka Territory (including any maintenance fees owed to local patent offices for the Joint
                Collaboration Patent Rights in the Otsuka Territory), and Otsuka will reimburse Ionis for such costs within [***] after receiving an invoice with reasonable supporting documentation for such costs.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5e5ca68a57cb49f383779b2ed45e15c9">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Review and Consult</font>. Ionis will consult with Otsuka and keep Otsuka reasonably informed regarding the Patent Prosecution of the Ionis Product-Specific Patents in the Otsuka Territory and the Patent
                Prosecution of the Joint Collaboration Patent Rights worldwide and will provide Otsuka with all substantive correspondence received from any patent authority in connection therewith no later than [***] after receipt thereof. In addition,
                Ionis will provide Otsuka with drafts of proposed substantive filings in the Otsuka Territory and correspondence to any patent authority in the Otsuka Territory in connection with the Patent Prosecution of the Ionis Product-Specific Patents
                and with drafts of proposed substantive filings in the Territory and correspondence to any patent authority in the Territory in connection with the Patent Prosecution of Joint Collaboration Patent Rights, in each case for Otsuka&#8217;s review
                and comment at least [***] prior to the submission of such proposed filings and correspondence, which comments (if any) Otsuka must provide no later than [***] after receipt of the applicable filing or correspondence. Ionis will consider in
                good faith Otsuka&#8217;s reasonable comments on the Patent Prosecution of the Ionis Product-Specific Patents in the Otsuka Territory and the Joint Collaboration Patent Rights in the Territory, but Ionis will have final decision-making authority
                regarding Patent Prosecution of such Patent Rights under this <u>Section 10.2.1(b)</u> (Review and Consult).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">46</font></div>
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      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7580d048e0b04b6ba5f9211a78b988aa">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Abandonment</font>. If, at any time during the Term, Ionis decides to cease the Patent Prosecution of a particular Ionis Product-Specific Patent in the Otsuka Territory, or a particular Joint
                Collaboration Patent Right in the Territory, then Ionis will provide written notice to Otsuka of such decision at least [***] prior to the date that such applicable Patent Right will become abandoned. Unless such written notice includes a
                reasonable strategic reason for ceasing such Patent Prosecution (<font style="font-style: italic;">e.g.</font>, continuing such Patent Prosecution would adversely affect Ionis&#8217; Patent Prosecution or litigation strategy), Otsuka may, upon
                written notice to Ionis, assume the Patent Prosecution of any such Patent Right at Otsuka&#8217;s sole cost and expense. Without limiting the foregoing, with respect to any such Joint Collaboration Patent Right abandoned by Ionis, Ionis shall
                assign, and hereby does assign, to Otsuka all of its rights, title and interests in and to such Joint Collaboration Patent Right, and upon such assignment, such Joint Collaboration Patent Right shall be deemed an Otsuka Patent Right for all
                purposes of this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0c20b336043c496993fd40d9ed359aa7">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.2.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Patent Rights</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf78fb4b1cd2849f6a216cd39dbc4360f">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Right to Prosecute</font>. As between the Parties, Otsuka will have the first right to control the Patent Prosecution of all Otsuka Patent Rights throughout the world. Otsuka will be responsible for [***]
                of the costs and expenses incurred with respect to the Patent Prosecution of such Patent Rights throughout the world.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z41ed06a4e56042f6b35c626517287b6f">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Review and Consult</font>. Otsuka will consult with Ionis and keep Ionis reasonably informed regarding the Patent Prosecution of the Otsuka Patent Rights and will provide Ionis with all substantive
                correspondence received from any patent authority in connection therewith no later than [***] after receipt thereof. In addition, Otsuka will provide Ionis with drafts of all proposed substantive filings and correspondence to any patent
                authority in connection with the Patent Prosecution of the Otsuka Patent Rights for Ionis&#8217; review and comment at least [***] prior to the submission of such proposed filings and correspondence, which comments (if any) Ionis must provide no
                later than [***] after receipt of the applicable filing or correspondence. Otsuka will consider in good faith Ionis&#8217; reasonable comments on the Patent Prosecution of the Otsuka Patent Rights, but will have final decision-making authority
                regarding Patent Prosecution of such Patent Rights under this <u>Section 10.2.2(b)</u> (Review and Consult).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z309ff21a755d40c1951c5eeb63065ee2">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Abandonment</font>. If, at any time during the Term, Otsuka ceases the Patent Prosecution of a particular Otsuka Patent Right, then Otsuka will provide written notice to Ionis of such decision at least
                [***] prior to the date on which such Patent Right will become abandoned. Unless such written notice includes a reasonable strategic reason for ceasing such Patent Prosecution (<font style="font-style: italic;">e.g.</font>, continuing such
                Patent Prosecution would adversely affect Otsuka&#8217;s Patent Prosecution or litigation strategy), Ionis may, upon written notice to Otsuka, assume the Patent Prosecution of any such Patent Right at Ionis&#8217; sole cost and expense.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">47</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
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      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z66698ed0094f4b388f5156bf7f5cfa53">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Enforcement Against Third Party Infringement or Misappropriation</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5610830ab7bb4c4fa21c002c8d628086">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.3.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Notice of Infringement or Misappropriation</font>. Each Party will promptly notify the other of any apparent, threatened, or actual Competitive Infringement of which it becomes aware.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5b3fafec1bb048acabf4ec716ff006d6">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.3.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka&#8217;s Enforcement Right</font>. Otsuka will have the first right, but not the obligation, to enforce [***] against any Competitive Infringement in the Otsuka Territory and at its own cost and expense
                and using counsel of its own choice; <font style="font-style: italic;">provided </font>that, (a) [***], Ionis will be entitled to attend any substantive meetings, hearings, or other proceedings related to such infringement or
                misappropriation suit (together with its own counsel, at its own expense) and to review and comment on all substantive documents related to such infringement or misappropriation suit prior to filing or submission of such documents, and (b)
                with respect to [***], Otsuka shall keep Ionis reasonably informed of the status of any substantive meetings, hearings, or other proceedings related to such infringement or misappropriation suit. If Otsuka fails to initiate a suit or take
                other action to abate any such Competitive Infringement within the earlier of: (i) [***] and (ii) [***], then, in either case, Ionis will have the second right, but not the obligation, to attempt to resolve such Competitive Infringement, at
                its own expense, including the filing of an infringement or misappropriation suit, as applicable, to enforce the applicable Patent Rights or Know-How using counsel of its own choice; <font style="font-style: italic;">provided </font>that,
                if Otsuka notifies Ionis during [***] that it is electing not to take steps to enforce the applicable Patent Rights against such Competitive Infringement [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z18cb88e0cf924a338a7728793093538a">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.3.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ionis&#8217; Enforcement Right</font>. Ionis will have the sole right, but not the obligation, to enforce [***] against any Competitive Infringement in the Territory, in each case ((a) and (b)), at its own cost
                and expense and using counsel of its own choice; <font style="font-style: italic;">provided </font>that Ionis shall keep Otsuka reasonably informed of the status of any substantive meetings, hearings, or other proceedings related to any
                infringement or misappropriation suit to enforce [***] against any Competitive Infringement in the Otsuka Territory. Ionis will have the first right, but not the obligation, to enforce any [***] in the Ionis Territory, in each case, at its
                own expense and using counsel of its own choice; <font style="font-style: italic;">provided </font>that Otsuka will be entitled to attend any substantive meetings, hearings, or other proceedings related to such infringement or
                misappropriation suit (together with its own counsel, at its own expense) and to review and comment on all substantive documents related to such infringement or misappropriation suit prior to filing or submission of such documents. If Ionis
                fails to initiate a suit or take other action to abate any such Competitive Infringement with respect to [***] in the Ionis Territory within the earlier of: (i) [***] and (ii) [***], then, in either case, Otsuka will have the second right,
                but not the obligation, to attempt to resolve such Competitive Infringement, at its own expense, including the filing of an infringement or misappropriation suit, as applicable, to enforce the applicable Otsuka Technology or Joint
                Collaboration Technology using counsel of its own choice; <font style="font-style: italic;">provided </font>that, if Ionis notifies Otsuka during [***] that it is electing not to take steps to enforce the applicable Patent Rights against
                such Competitive Infringement [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfd2b262635394dd78922cb78e85544b8">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.3.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Allocation of Recoveries</font>. Any recoveries resulting from an enforcement action relating to a claim of Competitive Infringement in the Territory will be first applied against payment of each Party&#8217;s
                costs and expenses in connection therewith. Any such recoveries in excess of such costs and expenses will be [***]; <font style="font-style: italic;">provided</font> that [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">48</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc3900b32fcd6481cbdad0f520baaa8e0">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.3.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Cooperation; Procedures</font>. At the request and expense of the Party bringing an infringement or misappropriation action under this <u>Section 10.3</u> (Enforcement Against Third Party Infringement or
                Misappropriation), the other Party will provide reasonable assistance and cooperation in any such action (including entering into a common interest agreement if reasonably deemed necessary by any Party) and agrees to be joined as a party to
                the suit if necessary for the initiating Party to bring or continue an infringement or misappropriation action hereunder. In addition, the Party bringing an infringement or misappropriation action under this <u>Section 10.3</u>
                (Enforcement Against Third Party Infringement or Misappropriation) will provide the other Party with copies of all pleadings and other documents in advance of filing with the court and will consider reasonable input from the other Party
                during the course of the action. For clarity, the Party bringing an infringement or misappropriation action under this <u>Section 10.3</u> (Enforcement Against Third Party Infringement or Misappropriation) will control such infringement or
                misappropriation action subject to the terms of this <u>Section 10.3</u> (Enforcement Against Third Party Infringement or Misappropriation). Neither Party may settle any action or proceeding brought under this <u>Section 10.3</u>
                (Enforcement Against Third Party Infringement or Misappropriation) or knowingly take any other action in the course thereof that disclaims, limits the scope of, admits the invalidity or unenforceability of, or grants a license, covenant not
                to sue or similar immunity under a Patent Right Controlled by the other Party without first obtaining the written consent of the Party that Controls the relevant Patent Right. Furthermore, Ionis may not [***]. The Parties will reasonably
                assist each other and cooperate with each other, at their own expense, in any such investigation, pre-litigation preparation, or litigation to ensure that there is an aligned global litigation and enforcement strategy.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zbf5969c925724890922a35fa406e716c">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Defense of Third-Party Patent Challenges</font>. Each Party will promptly notify the other Party in writing after becoming aware of an actual or threatened Patent Challenge by a Third Party of any Ionis
                Patent Right, Otsuka Patent Right, and Joint Collaboration Patent Right (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Third Party Patent Challenge</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z74185b6a8df948d8b6dd2020f524ea28">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.4.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka&#8217;s Right to Defend</font>. Subject to the terms of <u>Section 10.4.3</u> (Cooperation; Procedures), and except as may be otherwise agreed by the Parties, Otsuka will have the first right, but not
                the obligation, to control the defense of any Third Party Patent Challenge relating to an Otsuka Patent Right or Joint Collaboration Patent Right in the Otsuka Territory, and to compromise, litigate, settle, or otherwise dispose of any such
                challenge, in each case at its own expense using counsel of its own choice; <font style="font-style: italic;">provided </font>that (a) with respect to a Joint Collaboration Patent Right, Ionis will be entitled to attend any substantive
                meetings, hearings, or other proceedings related to such Third Party Patent Challenge (together with its own counsel, at its own expense) and to review and comment on all substantive documents related to such Third Party Patent Challenge,
                and (b) with respect to an Otsuka Patent Right, Otsuka shall keep<font style="font-style: italic;">&#160;</font>Ionis reasonably informed of the status of any substantive meetings, hearings, or other proceedings related to such Third Party
                Patent Challenge, and if Otsuka fails to initiate the defense of such Third Party Patent Challenge of a Patent Right in the Otsuka Territory within [***] after the notice provided under <u>Section 10.4</u> (Defense of Third Party Patent
                Challenges), or otherwise abandons or elects not to continue any such defense once initiated, then Ionis will have the second right, but not the obligation, to control the defense of such Third Party Patent Challenge at its own expense
                using counsel of its own choice.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">49</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
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      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5570bf40fd0043a286ad56040d3c61e1">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.4.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ionis&#8217; Right to Defend</font>. Ionis will have the sole right, but not the obligation, to control the defense of any Third Party Patent Challenge relating to an (a) Ionis Product-Specific Patent in the
                Ionis Territory or (b) Ionis Core Technology Patent or Ionis Manufacturing and Analytical Patent in the Territory, and to compromise, litigate, settle, or otherwise dispose of any such challenge, in each case, at its own expense using
                counsel of its own choice. Subject to the terms of <u>Section 10.4.3</u> (Cooperation; Procedures), Ionis will have the first right, but not the obligation, to control the defense of any Third Party Patent Challenge relating to an (i)
                Otsuka Patent Right or Joint Collaboration Patent Right in the Ionis Territory or (ii) Ionis Product-Specific Patent in the Otsuka Territory and to compromise, litigate, settle, or otherwise dispose of any such challenge, at its own expense
                using counsel of its own choice; <font style="font-style: italic;">provided </font>that Otsuka will be entitled to attend any substantive meetings, hearings, or other proceedings related to such Third Party Patent Challenge (together with
                its own counsel, at its own expense) and to review and comment on all substantive documents related to such Third Party Patent Challenge. If Ionis fails to initiate the defense of such Third Party Patent Challenge of an Otsuka Patent Right
                or Joint Collaboration Patent Right in the Ionis Territory or an Ionis Product-Specific Patent in the Otsuka Territory, in each case, within [***] after the notice provided under <u>Section 10.4</u> (Defense of Third Party Patent
                Challenges), or otherwise abandons or elects not to continue any such defense once initiated, then Otsuka will have the second right, but not the obligation, to control the defense of such Third Party Patent Challenge at its own expense
                using counsel of its own choice.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za1f7cae7a81946fbaa498bea9aebdd44">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.4.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Cooperation; Procedures</font>. At the request and expense of the Party controlling the defense of any Third Party Patent Challenge under this <u>Section 10.4</u> (Defense of Third Party Patent
                Challenges), the other Party will provide reasonable assistance and cooperation in any such action. In addition, the Party controlling the defense of any Third Party Patent Challenge under this <u>Section 10.4</u> (Defense of Third Party
                Patent Challenges) will provide the other Party with copies of all pleadings and other documents to be filed with the court and will consider reasonable input from the other Party during the course of the action. Otsuka may not settle any
                action or proceeding brought or defended under this <u>Section 10.4</u> (Defense of Third-Party Patent Challenges) or knowingly take any other action in the course thereof without Ionis&#8217; prior written consent, unless such action or
                proceeding solely concerns the Otsuka Patent Rights. Ionis may not settle any action or proceeding brought or defended under this <u>Section 10.4</u> (Defense of Third-Party Patent Challenges) or knowingly take any other action in the
                course thereof with respect to the Ionis Product-Specific Patents or Joint Collaboration Patent Rights in the Otsuka Territory, without Otsuka&#8217;s prior written consent not to be unreasonably withheld, conditioned or delayed. The Parties will
                reasonably assist each other and cooperate with each other, at their own expense, in any such investigation, pre-litigation preparation, or litigation to ensure that there is an aligned global litigation strategy. Notwithstanding the above,
                in the case of any invalidity or unenforceability claims arising in an enforcement action under <u>Section 10.3</u> (Enforcement Against Third Party Infringement or Misappropriation), the Party controlling the enforcement action pursuant
                to <u>Section 10.3</u> (Enforcement Against Third Party Infringement or Misappropriation) shall control the response to such invalidity or unenforceability claims, <font style="font-style: italic;">provided</font> such Party may not admit
                invalidity or unenforceability of any Patent Right Controlled by the other Party without the prior written consent of the other Party.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">50</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zddb021bca004444982219253dfb1e9d3">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Third Party Infringement Claims</font><font style="color: rgb(0, 0, 0);">.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1b8eca8f89994da4b47b4f8e7437ebdd">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.5.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Infringement Claim; Patent Challenges of Third-Party IP</font>. If a Third Party asserts that a Patent Right controlled by it is, or will be, infringed by the Exploitation of a Licensed Product in the
                Territory in accordance with this Agreement, then the Party first obtaining knowledge of such claim will promptly provide the other Party with prompt written notice thereof and the related facts in reasonable detail.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zed4652e11b66413d800dae1ce0fdffb8">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.5.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Responsibility to Defend</font>. During the Term of this Agreement, if a Third Party asserts that a Patent Right controlled by such Third Party is infringed, or will be infringed, by the Exploitation of a
                Licensed Product, then the Parties will promptly discuss the matter and the appropriate course of action. If the Parties cannot agree on a course of action within [***] following the date on which the Parties receive notice of such Third
                Party claim, then, subject to <u>Article 13</u> (Indemnification): (a) Ionis will have the sole right, but not the obligation, to defend such claim in the Ionis Territory using counsel of its own choosing, and (b) Otsuka will have the
                first right, but not the obligation, to defend such claim in the Otsuka Territory using counsel of its own choosing. If Otsuka does not take affirmative steps to defend such claim in the Otsuka Territory within [***] (or such shorter period
                of time as is legally required to answer to such claim) and does not inform Ionis within such [***] period that it is electing not to defend such claim for strategic reasons intended to maintain the commercial value of the relevant Patent
                Rights or any product or subject matter Covered thereby or relating thereto, then Ionis may defend such claim in the Otsuka Territory. The Party defending such claim in the Otsuka Territory will (i) keep the other Party reasonably informed
                regarding any such assertion, including by providing the other Party with copies of all pleadings and other documents filed in any proceeding relating to such claim, (ii) consider reasonable input from the other Party during the course of
                the claim, and (iii) provide the other Party with the opportunity to attend any substantive meetings, hearings, or other proceedings related to such claim (together with its own counsel, at its own expense) and to review and comment on all
                substantive documents related to such claim prior to filing or submission of such documents. The Parties will reasonably assist each other and cooperate and share information with respect to any such claim. Each Party will bear its own
                costs and expenses with respect to any such claim.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z86a80645006a493682b7199dd5259486">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.5.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Settlement</font>. Subject to <u>Article 13</u> (Indemnification), neither Party will pursue or enter into any settlement or license agreement with any Third Party with respect to the Patent Rights that
                are the subject of a claim brought by a Third Party that a Patent Right controlled by such Third Party is infringed by the Exploitation of a Licensed Product in the Otsuka Territory without the other Party&#8217;s prior written consent, not to be
                unreasonably withheld, conditioned, or delayed. Subject to <u>Article 13</u> (Indemnification), Otsuka will bear the costs of any amounts paid in settlement or to satisfy a judgment of a claim that the Exploitation of a Licensed Product
                infringes any Third Party Patent Right in the Otsuka Territory, except to the extent such costs [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z52143d0bc74e43ce8970911ef924a139">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.6</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Patent Challenges of Third-Party Patent Rights</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5ca2415db5034316845be0404f4b6330">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.6.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Notice of Third-Party Patent Right</font>. If either Party becomes aware of a Third Party Patent Right that might form the basis for a claim that the Exploitation of a Licensed Product anywhere in the
                world infringes, or will infringe, such Patent Right, then the Party first obtaining knowledge of such Patent Right will promptly provide the other Party with written notice thereof and the related facts in reasonable detail, and the
                Parties will promptly meet to discuss the matter.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">51</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z306b8abe3c6a433e88831de469eb647c">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.6.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Patent Challenges of Third-Party Patents</font>. Ionis will have the sole right, but not the obligation, to initiate a Patent Challenge of any such Third Party Patent Right in the Ionis Territory using
                counsel of its own choosing. Otsuka will have the first right, but not the obligation, to initiate a Patent Challenge of such Third Party Patent Right in the Otsuka Territory, and if Otsuka notifies Ionis that it does not intend to initiate
                such a Patent Challenge, Ionis will have the second right, but not the obligation, to do so; <font style="font-style: italic;">provided </font>that, [***]. The Party initiating such Patent Challenge will (a) keep the other Party
                reasonably informed regarding any such Patent Challenge, including by providing the other Party with copies of all pleadings and other documents filed in any proceeding relating to such Patent Challenge, (b) consider reasonable input from
                the other Party during the course of the Patent Challenge, and (c) provide the other Party with the opportunity to attend any substantive meetings, hearings, or other proceedings related to such Patent Challenge (together with its own
                counsel, at its own expense) and to review and comment on all substantive documents related to such Patent Challenge prior to filing or submission of such documents. The Parties will reasonably assist each other and cooperate and share
                information with respect to any such Patent Challenge. Each Party will bear its own costs and expenses with respect to any such Patent Challenge; <font style="font-style: italic;">provided, however,</font> that the Parties will each bear
                [***] of the reasonable out-of-pocket costs incurred with respect to any such Patent Challenge in the Otsuka Territory, and the non-controlling Party will reimburse the Party initiating such Patent Challenge in the Otsuka Territory for such
                costs within [***] after receiving an invoice with reasonable supporting documentation for such costs.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd39df9ae57a94070a00dde22ca9f550c">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.6.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Restrictions on Settlement</font>. Neither Party nor its Affiliates will pursue or enter into any settlement or license agreement with any Third Party with respect to the Patent Rights that are the
                subject of such Patent Challenge in the Otsuka Territory without the other Party&#8217;s prior written consent.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc65c530f915246ba8b0c663599b2674c">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.7</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Patent Term Extensions</font>. With respect to any system for extending the term of Patent Rights in the Otsuka Territory established by any applicable Regulatory Authority or patent office during the
                Term that is similar to the patent term extension system in the U.S., [***] for making all decisions regarding patent term extensions of the Ionis Patent Rights or Joint Collaboration Patent Rights in the Otsuka Territory, including
                supplementary protection certificates and any other extensions that are now or become available in the future, that are applicable to the Ionis Patent Rights or Joint Collaboration Patent Rights licensed hereunder and that become available
                directly as a result of the Regulatory Approval of a Licensed Product in the Otsuka Territory; <font style="font-style: italic;">provided</font> that Otsuka will consult with Ionis with respect to such decisions and consider in good faith
                the reasonable comments and concerns of Ionis.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze278d96a93d7406b96b67a4b6a74102e">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.8</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Unified Patent Court; Patent Linkage Listing</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z963416f5d1c84ebba4dbc505db262f05">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.8.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Otsuka will be solely responsible for making all decisions regarding the opting-out or opting-in of existing Patent Rights into the jurisdiction of the Unified Patent Court or the registration of Patent Rights with Unitary Effect; <font style="font-style: italic;">provided </font>that Otsuka will consult with Ionis with respect to such decisions and will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z73aca0c8045c4ea4bf6666ba18638318">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.8.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Otsuka will be solely responsible for making all decisions regarding the patent linkage listings (or other listings similar to the Orange Book listings in the U.S.) in the Otsuka Territory; <font style="font-style: italic;">provided </font>that




                Otsuka will consult with Ionis with respect to such decisions and will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">52</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z09d6958051234d0297144232f74a592b">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.9</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Common Interest</font>. The Parties stipulate and agree that, with regard to such prosecution, maintenance, enforcement, and defense the interests of the Parties as collaborators and licensor and licensee
                are to obtain the strongest patent protection possible, and as such, are aligned and are legal in nature. The Parties stipulate and agree that they have not waived, and nothing in this Agreement constitutes a waiver of, any legal privilege
                concerning the Patent Rights under this <u>Article 10</u> (Intellectual Property), including privilege under the common interest doctrine and similar or related doctrines. Notwithstanding any provision to the contrary set forth in this
                Agreement, to the extent a Party has a good faith belief that any information required to be disclosed by such Party to the other Party under this <u>Article 10</u> (Intellectual Property) is protected by attorney-client privilege or any
                other applicable legal privilege or immunity, such Party will not be required to disclose such information and the Parties will in good faith cooperate to agree upon a procedure (including entering into a specific common interest agreement,
                disclosing such information on a &#8220;for counsel eyes only&#8221; basis or similar procedure) under which such information may be disclosed without waiving or breaching such privilege or immunity.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z447a40301f0146cfb7c1d0f58f5d1aea">

          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.10</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Product Trademarks</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z22b6c6679a004c138de8d04c2edb99c4">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.10.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ownership</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z10801d533c444731a7a6f0bf490c0bbe">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Unitary Product Trademarks</font>. Ionis shall, at its sole cost and expense, develop, and shall use Commercially Reasonable Efforts to obtain and maintain, a unitary Trademark (and back-up Trademarks
                thereof) to be used for the Licensed Products worldwide (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Unitary Product Trademark</font>&#8221;); <font style="font-style: italic;">provided however</font>, [***]. If Otsuka believes
                it is necessary or reasonably useful to develop Trademarks in local languages in the Otsuka Territory (such as a katakana Trademark, which is a Japanese notation of a Trademark to be used for Exploitation of Licensed Products in Japan),
                Otsuka will [***] (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Local Unitary Product Trademark</font>&#8221;) will be deemed to be a Unitary Product Trademark for all purposes of this Agreement (including, for clarity, [***]).
                For clarity, it would be [***]. Ionis will own all right, title, and interest in and to each Unitary Product Trademark (including each Local Unitary Product Trademark). Otsuka will use the Unitary Product Trademarks in the Otsuka Territory
                to the extent required by and in accordance with the Otsuka Territory Brand Strategy, subject to <u>Section 6.4.1</u> (Global Brand Strategy and American Commercialization Operating Plan) and <u>Section 6.4.2</u> (Otsuka Territory Brand
                Strategy and Commercialization Operating Plans).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb4edf6e0bfc54ddca1cd744f655acffc">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ownership of Otsuka Product Trademarks</font>. As between the Parties, Otsuka will have the sole right to determine and will own all right, title, and interest in and to any Trademarks, other than the
                Unitary Product Trademarks, to be created or used by Otsuka or its Affiliates or its or their Sublicensees for the Exploitation of Licensed Product in the Otsuka Territory excluding any trademarks, service marks, names, or logos that
                include any corporate name or logo of the Parties or their Affiliates or its or their Sublicensees (&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Product Trademarks</font>&#8221;); <font style="font-style: italic;">provided </font>that




                such Otsuka Product Trademarks are consistent with the Global Brand Strategy, except to the extent such inconsistency is (i) [***], or (ii) [***]. Ionis will not [***]. Ionis will not [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">53</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z87aa07f9147640f698bc81f595f268ed">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ownership of Ionis Product Trademarks</font>. As between the Parties, Ionis will have the sole right to determine and will own all right, title, and interest in and to the Trademarks (other than the
                Unitary Product Trademarks) to be used by Ionis or its Affiliates or its or their Sublicensees or licensees for the Exploitation of Licensed Product in the Ionis Territory excluding any trademarks, service marks, names, or logos that
                include any corporate name or logo of the Parties or their Affiliates or its or their Sublicensees or licensees (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product Trademarks</font>&#8221;); <font style="font-style: italic;">provided</font>
                that such Ionis Product Trademarks are consistent with the Global Brand Strategy.<font style="font-weight: bold; font-style: italic;">&#160;</font>Otsuka will not [***]. Otsuka will not [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z980a8b1bea8f43c0a465699755be2224">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.10.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Notice</font>. Each Party will provide to the other Party prompt written notice of any actual or threatened infringement of the Otsuka Product Trademarks or Ionis Product Trademarks in the Territory and
                of any actual or threatened claim that the use of the Otsuka Product Trademarks or Ionis Product Trademarks in the Territory violates the rights of any Third Party, in each case, of which such Party becomes aware.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf33f80941e664ebd822aedd355c7a65d">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.10.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Prosecution of Product Trademarks</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc9e2ab349aad4a56aaf2e01979ebe4a0">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Unitary Product Trademarks</font>.<font style="font-weight: bold;">&#160;</font>Ionis shall be responsible, at its sole discretion and cost and expense using counsel of its own choice, for the filing,
                prosecution, registration, and maintenance (including the defense of opposition proceedings and any equivalent proceedings and including any legal actions to prevent or exclude Third Party Trademark registrations that are confusingly
                similar to any Unitary Product Trademark) of the Unitary Product Trademarks in the Territory (including the Local Unitary Product Trademarks in the Otsuka Territory) throughout the Term. Ionis shall keep Otsuka informed of material progress
                with regard to the prosecution, registration, and maintenance of the Unitary Product Trademarks in the Otsuka Territory, including the content and timing of the filing of the Unitary Product Trademarks in the Otsuka Territory, [***], and
                Ionis shall [***] the Unitary Product Trademarks in the Otsuka Territory<font style="font-weight: bold; font-style: italic;">.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zbd8d0695233346018682c37deaf8b661">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Product Trademarks</font>. Otsuka will have the sole right to register, prosecute and maintain the Otsuka Product Trademarks in the Territory using counsel of its own choice. All costs and expenses
                of registering, prosecuting, and maintaining the Otsuka Product Trademarks in the Territory will be borne solely by Otsuka.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zcd340231371c4844b42b5ff48d73c3cd">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ionis Product Trademarks</font>. Ionis will have the sole right to register, prosecute and maintain the Ionis Product Trademarks in the Territory using counsel of its own choice. All costs and expenses of
                registering, prosecuting, and maintaining the Ionis Product Trademarks in the Territory will be borne solely by Ionis.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9803c1d66d964470a301deebfbe5c3b9">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.10.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Enforcement of Product Trademarks</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3776fb264b24415db47aa7d6ea238a8a">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Unitary Product Trademarks</font>.<font style="font-weight: bold;">&#160;</font>During the Term, each Party will promptly notify the other Party in writing of any alleged, threatened, or actual infringement,
                dilution, misappropriation or other violation of or unfair trade practices or any other like offense by a Third Party relating to any Unitary Product Trademark (including any Local Unitary Product Trademark) in the Otsuka Territory (&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory Trademark Infringement</font>&#8221;). Otsuka will have the first right, but not the obligation, to take any reasonable measures it deems appropriate with respect to any Otsuka
                Territory Trademark Infringement, using counsel of its own choice, and at its own cost and expense, including initiating or prosecuting an infringement, misappropriation or other appropriate suit or action to enforce the Unitary Product
                Trademarks in the Otsuka Territory and, if requested by Otsuka, Ionis shall (i) join as a party to such suit or action and execute and cause its Affiliates to execute all documents necessary for Otsuka to initiate and maintain such suit or
                action and (ii) provide reasonable assistance to Otsuka in connection with such suit or action. Notwithstanding the foregoing, if Otsuka does not inform Ionis that it intends to initiate a suit or take other action against an Otsuka
                Territory Trademark Infringement within [***] after Otsuka becoming aware of such Otsuka Territory Trademark Infringement and does not [***] within such [***], then Ionis will have the second right, but not the obligation, to initiate a
                suit or take other action against such Otsuka Territory Trademark Infringement at its own cost and expense. Any recoveries resulting from such suit or other action will be first applied against payment of each Party&#8217;s costs and expenses in
                connection therewith. Any such recoveries in excess of such costs and expenses will be [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">54</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za60a1ab6728c4cdaadedb73430adafbd">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Product Trademarks</font>. Otsuka will have the sole right to take such action as Otsuka deems necessary against a Third Party based on any alleged, threatened, or actual infringement, dilution,
                misappropriation or other violation of or unfair trade practices or any other like offense relating to, the Otsuka Product Trademarks by a Third Party in the Territory, at its sole cost and expense and using counsel of its own choice.
                Otsuka will retain any damages or other amounts collected in connection therewith.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z13e7ca32b978454eb03d3bf08c14a38a">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ionis Product Trademarks</font>. Ionis will have the sole right to take such action as Ionis deems necessary against a Third Party based on any alleged, threatened, or actual infringement, dilution,
                misappropriation or other violation of or unfair trade practices or any other like offense relating to, the Ionis Product Trademarks by a Third Party in the Territory, at its sole cost and expense and using counsel of its own choice. Ionis
                will retain any damages or other amounts collected in connection therewith.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z60f73886ace84521b72122f30bb17582">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.10.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Third Party Claims</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb48046095b374a3e9afabee731216c62">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Unitary Product Trademarks</font>. If a Third Party brings suit alleging that Otsuka&#8217;s or its Affiliate&#8217;s or Sublicensee&#8217;s Exploitation of a Licensed Product in the Otsuka Territory infringes or will
                infringe such Third Party&#8217;s Trademarks or that the use or registration of any Unitary Product Trademark (including any Local Unitary Product Trademark) in the Otsuka Territory infringes, dilutes, misappropriates or otherwise violates any
                Trademark or other right of such Third Party (&#8220;<font style="font-weight: bold; font-style: italic;">Trademark Infringement Suit</font>&#8221;), then the Party against whom such suit is brought will promptly notify the other Party of such
                Trademark Infringement Suit and Otsuka will have the first right, but not the obligation, to defend such Trademark Infringement Suit using counsel of its own choice. If Otsuka does not take affirmative steps to defend such Trademark
                Infringement Suit within [***] (or such shorter period of time as is legally required to answer to such suit) and does not [***], then Ionis may defend such Trademark Infringement Suit. The Party defending such Trademark Infringement Suit
                will (i) keep the other Party reasonably informed regarding such suit, including by providing the other Party with copies of all pleadings and other documents filed in any proceeding relating to such suit, (ii) consider reasonable input
                from the other Party during the course of the suit, and (iii) provide the other Party with the opportunity to attend any substantive meetings, hearings, or other proceedings related to such suit (together with its own counsel, at its own
                expense) and to review and comment on all substantive documents related to such suit prior to filing or submission of such documents. The Parties will reasonably assist each other and cooperate and share information with respect to any such
                suit. The Parties will [***] all of the costs incurred by either Party in defending a Trademark Infringement Suit and any and all damages paid in settlement or to satisfy a judgment in a Trademark Infringement Suit. Neither Party will enter
                into any settlement of a Trademark Infringement Suit that is instituted or threatened to be instituted against the other Party without the other Party&#8217;s prior written consent, not to be unreasonably withheld, conditioned or delayed; <font style="font-style: italic;">provided</font> that such consent will not be required if such settlement includes a release of all liability in favor of, and does not impose any obligation on, the other Party and contains no admission of
                liability by such settling Party. Further, neither Party shall settle or compromise any Trademark Infringement Suit, or knowingly take any other action in the course thereof, in a manner that materially adversely affects the other Party&#8217;s
                rights or interests, without the other Party&#8217;s prior written consent.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">55</font></div>
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8a481bf864a64baca28739191854d6bb">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Otsuka Product Trademarks</font>. Otsuka will have the sole right to defend against and settle any alleged, threatened or actual claim by a Third Party that the use or registration of the Otsuka Product
                Trademarks in the Territory infringes, dilutes, misappropriates or otherwise violates any Trademark or other right of that Third Party or constitutes unfair trade practices or any other like offense or any other claims as may be brought by
                a Third Party against a Party in connection with the use of the Otsuka Product Trademarks with respect to the Licensed Products in the Otsuka Territory, at its sole cost and expense and using counsel of its own choice. Otsuka will retain
                any damages or other amounts collected in connection therewith.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z96f3342768dc4232a91cca28dd0777a7">

          <tr>
            <td style="width: 75.6pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Ionis Product Trademarks</font>. Ionis will have the sole right to defend against and settle any alleged, threatened or actual claim by a Third Party that the use or registration of the Ionis Product
                Trademarks in the Territory infringes, dilutes, misappropriates or otherwise violates any Trademark or other right of that Third Party or constitutes unfair trade practices or any other like offense or any other claims as may be brought by
                a Third Party against a Party in connection with the use of the Ionis Product Trademarks with respect to the Licensed Products in the Ionis Territory, at its sole cost and expense and using counsel of its own choice. Ionis will retain any
                damages or other amounts collected in connection therewith.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za6c1fbb6047c4a4c9f463ec706158d85">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.10.6</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Housemarks</font>. The Parties, through the Europe JSC or the Asia JSC, in consultation with regulatory experts, will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zba4b0794dd30462c93688152f464706c">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">10.10.7</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Cooperation</font>. Each Party will, and will cause its Affiliates to, promptly assist and cooperate with the other Party, as may be reasonably requested by a Party from time to time, in connection with
                its activities set forth in this <u>Section 10.10</u> (Product Trademarks), including where necessary, furnishing a power of attorney solely for such purpose or joining in, or being named as a necessary party to, such action, and providing
                access to relevant documents and other evidence; <font style="font-style: italic;">provided</font> that, except as provided otherwise in this <u>Section 10.10</u> (Product Trademarks) with respect to [***], the requesting Party will
                reimburse the other Party for its [***] incurred in connection therewith.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">56</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
      </div>
      <div style="text-align: center;">
        <!--PROfilePageNumberReset%Num%57%%%--><font style="font-weight: bold;">ARTICLE 11</font></div>
      <div>
        <div>
          <div style="text-align: center; font-weight: bold;">REPRESENTATIONS, WARRANTIES, AND COVENANTS</div>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z17d3b6c1930e4ef5bc52d92dd5e6f8cd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Mutual Representations and Warranties</font>. Each of Otsuka and Ionis hereby represents and warrants to the other Party as of the Restatement Date that:</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z60ca24d4885b4e25b6175cccfa523d4b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.1.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>It is a corporation or limited company duly organized, validly existing, and in good standing under the laws of the jurisdiction of its organization, and it has the full right, power, and authority to enter into this Agreement and to
                    perform its obligations hereunder.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z370848acf94e402198906259154f075e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.1.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>All consents, approvals, and authorizations from all Governmental Authorities or other Third Parties required to be obtained by such Party in connection with this Agreement have been obtained.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z4c0d1893ff5a4e7d83cb502bbb6e3ba4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.1.3</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The execution, delivery, and performance of this Agreement by it has been duly authorized by all requisite corporate action.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="za96b7eef063544d4b3430b43bb318be0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.1.4</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The execution and delivery of this Agreement and the performance of its obligations hereunder (a) do not conflict with or violate any requirement of Applicable Law or any provision of its articles of incorporation, bylaws, limited
                    partnership agreement, or any similar instrument, as applicable, in any material way, and (b) do not conflict with, violate, or breach or constitute a default or require any consent under, any Applicable Law or any contractual
                    obligation or court or administrative order by which it is bound.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z098597bac6f94f5896d02c53df4fbed4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.1.5</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="color: rgb(0, 0, 0);">It has not been </font>debarred or suspended under 21 U.S.C. &#167;335(a) or (b)<font style="color: rgb(0, 0, 0);">, is not the subject of a conviction described in Section 306 of the FD&amp;C Act,</font>
                    has not been and is not excluded from a federal or governmental health care program, debarred from federal contracting, convicted of or pled <font style="font-style: italic;">nolo contendere</font> to any felony, or to any federal or
                    state legal violation (including misdemeanors) relating to prescription drug products or fraud, is not subject to OFAC sanctions or on the OFAC list of specially designated nationals, <font style="color: rgb(0, 0, 0);">and is not
                      subject to any similar sanction of any Governmental Authority in the Territory</font> (&#8220;<font style="font-weight: bold; font-style: italic;">Debarred/Excluded</font>&#8221;)<font style="color: rgb(0, 0, 0);">, and no proceeding that could
                      result in it being Debarred/Excluded is pending, and neither it nor any of its Affiliates has used, in any capacity in the performance of obligations relating to the Licensed Products, any </font>employee, <font style="color: rgb(0, 0, 0);">subcontractor, consultant, </font>agent, representative, <font style="color: rgb(0, 0, 0);">or other Person who has been Debarred/Excluded</font>.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zf65c75b94d914ba39b6addcd4f6b2122" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Additional Ionis Representations and Warranties</font>. Ionis hereby represents and warrants as of the Restatement Date to Otsuka that:</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z9ddd86f76de843f98a675328978ad02b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>It has the right under the Ionis Technology to grant to Otsuka the licenses in the Asia Territory set forth in this Agreement, and it has not granted any license or other right under the Ionis Technology that is inconsistent with the
                    licenses granted to Otsuka in the Asia Territory hereunder.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z164f08caa9334d9a9f15e2e7607ef340" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-variant: small-caps; color: rgb(0, 0, 0);"><u>Schedule 1.111</u></font><font style="color: rgb(0, 0, 0);"> (Ionis Core Technology Patents), </font><font style="font-variant: small-caps;"><u>Schedule 1.117</u></font>
                    (Ionis Manufacturing and Analytical Patents), and <font style="font-variant: small-caps;"><u>Schedule 1.124</u></font> (Ionis Product-Specific Patents), collectively, list all Ionis Patent Rights existing as of the Restatement Date.
                    With respect to any such Ionis Patent Right identified as being solely owned by Ionis, Ionis owns all rights, title, and interests in and to such Ionis Patent Rights.</div>
                </td>
              </tr>

          </table>
          <div> <br>
          </div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">57</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="z7f57ff3d5268448bbd02e07d8dfdd33d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.3</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>As of the Restatement Date, all issued Patent Rights in the Asia Territory within the Ionis Patent Rights are in full force and effect and, to Ionis&#8217; Knowledge, are valid and enforceable. To Ionis&#8217; Knowledge, all Ionis Patent Rights
                    in the Asia Territory<font style="font-size: 12pt;">&#160;</font>are being diligently prosecuted in the respective patent offices in the Asia Territory in accordance with Applicable Law and have been filed, prosecuted, and maintained
                    properly and correctly, and all applicable fees have been paid on or before the due date for payment.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z337ac2777c74404dbc70f1ba31b69d24" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.4</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>There is no pending or, to Ionis&#8217; Knowledge, threatened litigation, nor has Ionis received any written notice from any Third Party, asserting or alleging that the Exploitation of the Licensed Products in the Asia Territory prior to
                    the Restatement Date infringed or misappropriated the Patent Rights, Know-How or other intellectual property rights of such Third Party or that the disclosing, copying, making, assigning, licensing or use of the Ionis Technology in the
                    Asia Territory infringes or misappropriates any Patent Right, Know-How or other intellectual property rights of such Third Party.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="za62af8af8ff24d75adb58df46252c42f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.5</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>To Ionis&#8217; Knowledge, the practice by Otsuka of the Ionis Technology in the Asia Territory and the Exploitation by Otsuka or its Affiliates or Sublicensee of the Licensed Products in the Asia Territory in the form existing as of the
                    Restatement Date for the treatment of HAE, in each case, does not and will not infringe, misappropriate, or otherwise violate any Patent Rights, Know-How or other intellectual property rights of any Third Party.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="ze4d035d0fd964e09a80296b1a18eacc0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.6</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>To Ionis&#8217; Knowledge, there are no Third Party Know-How or Patent Rights that are necessary for the Exploitation of Licensed Products in the form existing as of the Restatement Date for the treatment of HAE in the Asia Territory,
                    other than the Know-How and Patent Rights licensed to Ionis pursuant to the Existing Third-Party IP Agreements. To Ionis&#8217; Knowledge, other than the Patent Rights and Know-How licensed to Ionis pursuant to the Existing Third-Party IP
                    Agreements, there are no Third Party Patent Rights in the Asia Territory that Cover the composition of matter of Licensed Compound or Licensed Products or any Third Party Patent Rights or Know-How in the Asia Territory that are used in
                    the Manufacture of the Licensed Product in the form existing as of the Restatement Date.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z7b92cc71522b40139fb374fe415dc9d8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.7</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>There are no pending or, to Ionis&#8217; Knowledge, threatened, adverse actions, suits, or proceedings against Ionis in the Asia Territory involving the Ionis Technology.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z6b2e5d4f089b472995b3bb725a00da38" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.8</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>To Ionis&#8217; Knowledge, no Person is infringing or threatening to infringe or misappropriating or threatening to misappropriate any Ionis Technology in the Asia Territory.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zb5575d627fc244eca708784288e0b0ba" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.9</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>There are no legal claims, judgments, or settlements against or owed by Ionis or any of its Affiliates, or pending or, to Ionis&#8217; Knowledge, threatened, legal claims or litigation, in each case, relating to antitrust,
                    anti-competition, or anti-corruption law violations in the Asia Territory.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z4224ef48af0c4547a1307fd7991f69d9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.10</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-variant: small-caps;"><u>Schedule</u></font><u> 1.69</u> (Existing Third-Party IP Agreements) sets forth all Existing Third-Party IP Agreements in effect as of the Restatement Date, redacted copies of which have
                    been provided to Otsuka prior to the date hereof. Other than the Existing Third-Party IP Agreements set forth in <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 1.69</u> (Existing Third-Party IP Agreements), as of the
                    Restatement Date there are no agreements between Ionis and any Third Party pursuant to which Ionis Controls any Know-How or Patent Rights in the Asia Territory within the Ionis Technology.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">58</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="zf69710d74c214a9b8da1b8eab5d8284f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.11</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Except for Existing Third-Party IP Agreements, Ionis is not obligated under any contract or other agreement with a Third Party as of the Restatement Date to make any payments to any owner or licensor of, or other claimant to, any
                    Patent Right, Know-How or other intellectual property or proprietary right with respect to the Exploitation of the Licensed Product in the Asia Territory in the form existing as of the Restatement Date for the treatment of HAE.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z8951d95d421943f9ab5215e25d5c7fdd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.12</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>With respect to the Existing Third-Party IP Agreements, Ionis represents and warrants to Otsuka, as of the Restatement Date, that: (a) it is in full force and effect; (b) neither Ionis nor any of its Affiliates is in material breach
                    thereof; (c) neither Ionis nor any of its Affiliates has received any notice from any counterparties thereto of any material breach or notice of threatened material breach thereof; (d) neither Ionis nor any of its Affiliates has
                    received any notice from any counterparties thereto of any intent to reduce the scope of the field thereunder or render any of the licenses thereunder non-exclusive or otherwise terminate such Existing Third-Party IP Agreements, and, to
                    Ionis&#8217; Knowledge no event, act or omission has occurred which would reasonably give rise to the right of any counterparties thereto to reduce the scope of the field thereof or render any of the licenses thereunder non-exclusive or
                    otherwise terminate such agreement or any licenses thereunder (including with respect to any particular Patent Rights or other intellectual property); (e) neither Ionis nor any of its Affiliates have waived or relinquished any rights
                    thereunder; (f) entering into this Agreement and granting the rights and licenses granted (or purported to be granted) to Otsuka hereunder complies with and will not result in a breach of the terms and conditions of any Existing
                    Third-Party IP Agreement; and (g) Ionis has the right to grant sublicenses to Otsuka under the Existing Third-Party IP Agreements as contemplated herein, including to Develop, Manufacture, Commercialize and conduct Medical Affairs for
                    the Licensed Products in the Field in the Asia Territory.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zfed8e9cd1cab46c6ac5da7bb4ad3270b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.13</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Neither Ionis nor any counterparty to any Existing Third-Party IP Agreement has in writing alleged or threatened that the other party has breached an Existing Third-Party IP Agreement (which has not been cured) or, to Ionis&#8217;
                    Knowledge, threatened in writing to terminate an Existing Third-Party IP Agreement.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z0abfa50ac715422d93ca55d14c6860fc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.14</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Each [***].</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z046cfee388f847c6979d3776bda8fb6d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.15</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>to Ionis&#8217; Knowledge: (a) [***]; and (b) [***].</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z0edd89c522aa4679979cec91405de589" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.16</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>All preclinical and clinical studies necessary for Regulatory Approval in the Asia Territory of the Licensed Products sponsored by Ionis or its Affiliates have been and as of the Restatement Date are being conducted in material
                    compliance with Applicable Law, including [***]. Neither Ionis nor its Affiliates has received any written notice from the PMDA or any other Regulatory Authority in the Asia Territory performing functions similar to those performed by
                    those with respect to any ongoing clinical or pre-clinical studies or tests of the Licensed Products requiring the termination, suspension, or material modification of such ongoing studies or tests, and no Governmental Authority in the
                    Asia Territory has commenced any action to place a clinical hold order on, or otherwise terminate or suspend, any ongoing Clinical Trial of the Licensed Products conducted by or on behalf of Ionis or its Affiliates necessary for
                    Regulatory Approval in the Asia Territory as of the Restatement Date.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">59</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="z96138b6a4537409f9cb280ef8c84f311" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.17</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>As of the Restatement Date, neither Ionis nor any of its Affiliates, and, to Ionis&#8217; Knowledge, none of its or their respective officers, employees, or agents, has made an untrue statement of material fact or fraudulent statement to
                    the PMDA or any other Regulatory Authority in the Asia Territory with respect to the Development of the Licensed Compounds or the Licensed Products in the Asia Territory, failed to disclose a material fact required to be disclosed to
                    the PMDA or any other Regulatory Authority in the Asia Territory with respect to the Development of the Licensed Compounds or the Licensed Products in the Asia Territory, or committed an act, made a statement, or failed to make a
                    statement with respect to the Development of the Licensed Compounds or the Licensed Products in the Asia Territory that could reasonably be expected to provide a basis for the PMDA to invoke any laws or policies in the Asia Territory
                    analogous to the FDA policy respecting &#8220;Fraud, Untrue Statements of Material Facts, Bribery, and Illegal Gratuities&#8221;, set forth in 56 Fed. Reg. 46191 (September 10, 1991).</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z23a6a6f08abb4482bee4cea10e4c11af" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.2.18</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>As of the Restatement Date, Ionis has no Knowledge of [***] in the Asia Territory in the form existing as of the Restatement Date for the treatment of HAE.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z14d7e422bc4b4eaeb77ff6ff73a766ff" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.3</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Additional Representations and Warranties</font>.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zb49634cf12624d4abe03e2e1c517a12b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.3.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Otsuka represents and warrants to Ionis as of the Restatement Date that there are no Patent Rights Controlled by Otsuka or any of its Affiliates that are necessary to Exploit a Licensed Product in the Asia Territory.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z322bc45b4d4849f5a30a3be123f3f078" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.3.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Ionis&#8217; representations and warranties set forth in Section 11.2 of the Original Agreement are hereby incorporated by reference in this Agreement in their entirety (with all such defined terms contained therein having the applicable
                    meanings set forth in the Original Agreement), with such representations and warranties being effective as of the Original Effective Date.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zd3692323f5ee4a7284446d1d3a0674d2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.4</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Additional Covenants</font>. Each of Otsuka and Ionis hereby covenant to the other:</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z373f179bfff04356b67fe91672770a3a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.4.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Assignment of Inventions</font>. Each Party will require all of its and its Affiliates&#8217; employees and consultants to assign all Inventions that are developed or invented by such employees according to
                    the ownership principles described in <u>Section 10.1</u> (Inventions).</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z614280ba0e204e209b720962988133ab" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.4.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Compliance with Law</font>. It will, and will ensure that its Affiliates, comply with all Applicable Law and, to the extent applicable, Professional Requirements, with respect to the performance of
                    its obligations under this Agreement, including, as applicable, the Approved Labeling,<font style="color: rgb(0, 0, 0);"> the European Data Protection Directive 95/46/EC, the European General Data Protection Regulation (Regulation (EU)
                      2016/679), and any other applicable national data protection legislation.</font></div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z47dd19ca0dcf4f2784ed17dffeb5fd98" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.4.3</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">No Bribery</font>. It will not in the future offer, promise, pay, authorize, or give, money or anything of value, directly or indirectly, to any Government Official or Other Covered Party for the
                    purpose, pertaining to this Agreement, of: (a) influencing any act or decision of the Government Official or Other Covered Party; (b) inducing the Government Official or Other Covered Party to do or omit to do an act in violation of a
                    lawful duty; (c) securing any improper advantage; or (d) inducing the Government Official or Other Covered Party to influence the act or decision of a government or government instrumentality, in order to obtain or retain business, or
                    direct business to, any Person, in each case, in any way related to this Agreement.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">60</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="z7f9bcf33b70b44a2a7815f4757401400" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.4.4</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Restricted Countries</font>. Neither it nor its Affiliates will export, transfer, or sell any Licensed Product (a) to any country or territory that is subject to comprehensive economic sanctions
                    administered by OFAC, unless the sale of such Licensed Product would be permissible if Otsuka or its Affiliates or Sublicensees were subject to OFAC&#8217;s jurisdiction, (b) to any other country or territory in which such activity would
                    violate Applicable Law in the U.S., (c) to any Restricted Party unless the sale of such Licensed Product would be permissible if Otsuka or its Affiliates or Sublicensees was subject to OFAC&#8217;s jurisdiction, or (d) in such a manner that
                    would violate the Global Trade Control Laws.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="za1dc95481ca042e89a867e530dd26c7d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.4.5</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">FCPA Compliance</font>. In performing under this Agreement, it and its Affiliates agree to comply with all applicable anti-corruption laws, including the Foreign Corrupt Practices Act of 1977<font style="color: rgb(0, 0, 0);"> and the UK Bribery Act 2010</font>, as amended from time-to-time; the anti-corruption laws of the Territory; and all laws enacted to implement the Organization for Economic Co-operation and Development
                    Convention on Combating Bribery of Foreign Officials in International Business Transactions.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="ze537a91afef4456e9d247499ae436be6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">11.4.6</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Debarred/Excluded Persons</font>. It will not engage, in any capacity in connection with this Agreement or any ancillary agreements, any officer, employee, contractor, consultant, agent,
                    representative, or other Person who has been Debarred/Excluded. Each Party will inform the other Party in writing promptly if it or any Person engaged by it or any of its Affiliates who is performing any obligations under this Agreement
                    or any ancillary agreements is Debarred/Excluded, or if any action, suit, claim, investigation, or legal or administrative proceeding is pending or, to each Party&#8217;s Knowledge, is threatened, pursuant to which a Party, any of its
                    Affiliates or any such Person performing obligations hereunder or thereunder may become Debarred/Excluded.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z1c8f9a72f538427eba89e972c250492c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.5</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Disclaimer</font>. EXCEPT AS EXPRESSLY SET FORTH HEREIN, THE INTELLECTUAL PROPERTY RIGHTS PROVIDED BY EACH PARTY ARE PROVIDED &#8220;AS IS&#8221; AND WITHOUT WARRANTY. EXCEPT AS EXPRESSLY SET FORTH HEREIN, EACH
                    OF THE PARTIES EXPRESSLY DISCLAIMS ANY AND ALL WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING THE WARRANTIES OF DESIGN, MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, VALIDITY, OR ENFORCEABILITY OF THEIR RESPECTIVE
                    INTELLECTUAL PROPERTY RIGHTS, AND NONINFRINGEMENT OF THE INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES, ARISING FROM A COURSE OF DEALING, USAGE, OR TRADE PRACTICES, IN ALL CASES WITH RESPECT THERETO.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="za22f08ac6c2d429baef1db339e2eff55" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.6</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Limitation of Liability</font>. NEITHER OF THE PARTIES WILL BE ENTITLED TO RECOVER FROM THE OTHER PARTY ANY SPECIAL, INCIDENTAL, INDIRECT, CONSEQUENTIAL, OR PUNITIVE DAMAGES OR DAMAGES FOR LOSS OF
                    PROFIT, LOSS OF REVENUE, OR LOST OPPORTUNITY IN CONNECTION WITH THIS AGREEMENT, ITS PERFORMANCE OR LACK OF PERFORMANCE HEREUNDER, OR ANY LICENSE GRANTED HEREUNDER, EXCEPT TO THE EXTENT THE DAMAGES RESULT FROM A BREACH OF THE OBLIGATIONS
                    OF A PARTY UNDER <u>ARTICLE 12</u> (CONFIDENTIALITY) OR BREACH OF <u>SECTION 2.5.2</u> (NEGATIVE COVENANT) BY IONIS, MISAPPROPRIATION OR INFRINGEMENT OF INTELLECTUAL PROPERTY OWNED OR CONTROLLED BY THE OTHER PARTY, OR AMOUNTS REQUIRED
                    TO BE PAID TO A THIRD PARTY AS PART OF A CLAIM FOR WHICH A PARTY PROVIDES INDEMNIFICATION UNDER <u>ARTICLE 13</u> (INDEMNIFICATION).</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">61</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
          </div>
          <div style="text-align: center; font-weight: bold;">ARTICLE 12</div>
          <div style="text-align: center; font-weight: bold;">CONFIDENTIALITY</div>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z95b778754c044ea196fcf2cdd12603ed" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Duty of Confidence</font>. Subject to the other provisions of this <u>Article 12</u> (Confidentiality):</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zb0e1ed055130495c8dc11c9640e02e8d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.1.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>except to the extent expressly authorized by this Agreement, the Receiving Party shall maintain in confidence and otherwise safeguard, and not publish or otherwise disclosed, all Confidential Information of the Disclosing Party;</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z6cea7fd0cbcc499f92a3b6971c1f107e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.1.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>the Receiving Party will treat all Confidential Information provided by the Disclosing Party, at a minimum, with the same degree of care as the Receiving Party uses for its own similar information, but in no event less than a
                    reasonable degree of care;</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z3f4129d9a3464295b7bd5c61141a10ca" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.1.3</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>the Receiving Party may only use any Confidential Information of the Disclosing Party for the purposes of performing its obligations or exercising its rights under this Agreement;</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z9853c8f0a9034265a06cebc06f2fb742" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.1.4</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>a Receiving Party may only disclose Confidential Information of the Disclosing Party to: (a) such Receiving Party&#8217;s Affiliates, licensees, and Sublicensees; and (b) employees, directors, officers, agents, contractors, attorneys,
                    accountants and consultants, of the Receiving Party and its Affiliates, licensees, and Sublicensees, in each case ((a) and (b)), to the extent reasonably necessary for the purposes of, and for those matters undertaken pursuant to, this
                    Agreement; <font style="font-style: italic;">provided </font>that such Persons are bound by legally enforceable obligations of confidentiality and non-use with respect to the Disclosing Party&#8217;s Confidential Information, no less
                    stringent than the confidentiality and non-use obligations set forth in this Agreement, except that the term of such obligation will be customary for such recipient of Confidential Information. Each Party will remain responsible for any
                    failure by its Affiliates, licensees, and Sublicensees, and its and its Affiliates&#8217;, licensees&#8217;, and Sublicensees&#8217; respective employees, directors, officers, agents, consultants, attorneys, accountants and contractors, in each case, to
                    treat such Confidential Information as required under this <u>Section 12.1</u> (Duty of Confidence) (as if such Persons were Parties directly bound to the requirements of this <u>Section 12.1</u> (Duty of Confidence)); and</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z69eeba030b164d03959c9f43fb70cff8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.1.5</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>each Party will promptly notify the other Party of any misuse or unauthorized disclosure of the other Party&#8217;s Confidential Information.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="za3676f5ccc55483da03e936dae35bf9c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.1.6</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The confidentiality, non-use, and non-disclosure obligations set forth in this <u>Section 12.1</u> (Duty of Confidence) will be in full force and effect from the Restatement Date until [***] after expiration or termination of this
                    Agreement, <font style="font-style: italic;">provided</font> that, with respect to any Know-How that is a trade secret and is identified as such by the Disclosing Party at the time of disclosure, the obligations of this <u>Section
                      12.1</u> (Duty of Confidence) will continue for so long as such Know-How remains a trade secret.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zc3b1f897d39d426c90db04e4db9a0311" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Confidential Information</font>. Notwithstanding anything to the contrary in the definition of &#8220;Confidential Information&#8221; set forth in <u>Appendix 1</u> (Definitions), the Ionis Product-Specific
                    Know-How, any ROFN Exercise Notice, the Joint Collaboration Know-How and the terms of this Agreement will be the Confidential Information of both Parties, with each Party deemed to be the Receiving Party of such information; <font style="font-style: italic;">provided</font> that Ionis Product-Specific Know-How will be deemed the Confidential Information of Ionis following any termination (but not expiration) of this Agreement. The Ionis Core Technology Know-How
                    and the Ionis Manufacturing and Analytical Know-How will be the Confidential Information of Ionis. The Otsuka Know-How will be the Confidential Information of Otsuka. Except as provided in <u>Section 12.4</u> (Authorized Disclosures)
                    and <u>Section 12.6</u> (Publicity; Use of Names), neither Party nor its Affiliates may disclose the existence or the terms of this Agreement.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">62</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="z5dac648525004f34b053b4bb65c9e955" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.3</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Exemptions</font>. Information of a Disclosing Party will not be Confidential Information of such Disclosing Party to the extent that the Receiving Party can demonstrate through competent evidence
                    that such information:</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zc2b0c8e46b8340ff8b82eb9070d61bfb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.3.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>was already known by the Receiving Party or any of its Affiliates without an obligation of confidentiality at the time of its receipt from the Disclosing Party, and not through a prior disclosure by or on behalf of the Disclosing
                    Party, as documented by the Receiving Party&#8217;s business records;</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zce63109c786748d2b2935b417c8b24bc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.3.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>was generally available to the public or otherwise part of the public domain before its receipt from the Disclosing Party;</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="ze1ff44ee544641348b14ac0837aa22d6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.3.3</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>became generally available to the public or otherwise part of the public domain after its disclosure by the Disclosing Party other than through any act or omission of the Receiving Party or any of its Affiliates or disclosees in
                    breach of this Agreement;</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zddca06ba7b6a4475a1e9cca0d60b4611" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.3.4</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>is subsequently disclosed to the Receiving Party or any of its Affiliates without obligation of confidentiality by a Third Party who may rightfully do so and is not under a conflicting obligation of confidentiality to the Disclosing
                    Party; or</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z2188824f0ded4e4faa15457bc9a63059" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.3.5</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>is developed by the Receiving Party or any of its Affiliates independently and without use of or reference to any Confidential Information received from the Disclosing Party, as documented by the Receiving Party&#8217;s business records.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div style="text-align: justify; margin-left: 36pt;">No combination of features or disclosures will be deemed to fall within the foregoing exclusions merely because individual features are published or available to the general public or in the
            rightful possession of the Receiving Party unless the combination itself and principle of operation are published or available to the general public or in the rightful possession of the Receiving Party.</div>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zd0f92aa6417945baabe7ef95a2434ae0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.4</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Authorized Disclosures</font>.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zbaf90e339a3948fca9a92b41c5951fa4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.4.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Permitted Circumstances</font>. Notwithstanding the obligations set forth in <u>Section 12.1</u> (Duty of Confidence), a Party may disclose the other Party&#8217;s Confidential Information (including this
                    Agreement and the terms herein) to the extent such disclosure is reasonably necessary in the following situations:</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z649a809ef5714e8aae8d0155f115ad0f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(a)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>the prosecution or enforcement of Ionis Patent Rights, Collaboration Patent Rights, or Otsuka Patent Rights, in each case, as contemplated by this Agreement;</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z8156826a2d5b4b37a4677335e1595ba0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(b)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Regulatory Submissions and other filings or communications with Governmental Authorities (including Regulatory Authorities), as necessary for the Exploitation of the Licensed Products in connection with the exercise of the rights and
                    the performance of the obligations of the applicable Party under this Agreement;</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">63</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="z75679341edfb413cb1ac992f1b186e48" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(c)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>disclosure of this Agreement, its terms, and the status and results of Exploitation of the Licensed Products to actual or <font style="font-style: italic;">bona fide</font> potential investors, acquirors, (sub)licensees (including
                    any counterparty to a Collaboration In-License), lenders, and other financial or commercial partners (including in connection with any royalty financing transaction), and their respective attorneys, accountants, banks, investors, and
                    advisors, solely for the purpose of evaluating or carrying out an actual or <font style="font-style: italic;">bona fide</font> potential investment, acquisition, (sub)license, debt transaction, or collaboration transaction; <font style="font-style: italic;">provided </font>that,<font style="font-style: italic;">&#160;</font>in each such case, (i) such Persons are bound by obligations of confidentiality and non-use, or subject to professional ethical obligations of
                    confidentiality, at least as stringent as those set forth <u>Article 12</u> (Confidentiality), except that the term of such obligation will be customary for such recipient of Confidential Information and such type of transaction and
                    (ii) the scope of any such disclosure is limited to the maximum extent practicable for the particular context in which it is being disclosed;</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zea289a8c482f43b4a57fac6bb6c2cdad" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(d)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>such disclosure is required to comply with Applicable Law (whether generally or in pursuit of an application for listing of securities) including the United States Securities and Exchange Commission or equivalent foreign agency or
                    regulatory body, or otherwise required by judicial or administrative process, <font style="font-style: italic;">provided </font>that in each such event, as promptly as reasonably practicable and to the extent not prohibited by
                    Applicable Law or judicial or administrative process, such Party will notify the other Party of such required disclosure and provide a draft of the disclosure to the other Party reasonably in advance of such filing or disclosure for the
                    other Party&#8217;s review and comment. The non-disclosing Party will provide any comments as soon as practicable, and the disclosing Party will consider in good faith any timely comments provided by the non-disclosing Party; <font style="font-style: italic;">provided </font>that the disclosing Party may or may not accept such comments in its reasonable discretion. Confidential Information that is disclosed in order to comply with Applicable Law or by judicial
                    or administrative process pursuant to this <u>Section 12.4.1(d)</u> (Permitted Circumstances), in each case, will remain otherwise subject to the confidentiality and non-use provisions of this <u>Article 12</u> (Confidentiality) with
                    respect to the Party disclosing such Confidential Information, and such Party will take all steps reasonably necessary, including seeking of confidential treatment or a protective order to the maximum extent permitted by Applicable Law
                    or Governmental Authority, to ensure the continued confidential treatment of such Confidential Information, and each Party will be responsible for its own legal and other external costs in connection with any such filing or disclosure
                    pursuant to this <u>Section 12.4.1(d)</u> (Permitted Circumstances); or</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zef13b6153e124d80910a8ea05f303294" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(e)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>disclosure pursuant to <u>Section 12.6</u> (Publicity; Use of Names).</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zf6790e79535d46c5a381568bd2e58194" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(f)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>If and whenever any Confidential Information is disclosed in accordance with this <u>Section 12.4</u> (Authorized Disclosures), such disclosure will not cause any such information to cease to be Confidential Information except to
                    the extent that such disclosure results in a public disclosure of such information (other than by breach of this Agreement).</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">64</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
          </div>
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              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.5</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Publications</font>.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="ze8dd76bda8b0467082186b766a89167b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.5.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Otsuka&#8217;s Right to Publish</font>. Otsuka will have the right to publicly present or publish any Clinical Trial data, non-clinical or preclinical data, or any associated results or conclusions
                    generated by or on behalf of Ionis or Otsuka pursuant to this Agreement (each such proposed presentation or publication, an &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Publication</font>&#8221;), [***]. If Otsuka desires to
                    publicly present or publish an Otsuka Publication in accordance with the foregoing sentence, then Otsuka will provide Ionis (including Ionis&#8217; Alliance Manager and all Ionis members of the JSC) with a copy of such proposed Otsuka
                    Publication as early as practicable but at least [***] prior to the earlier of its presentation or intended submission for publication (such applicable period, the &#8220;<font style="font-weight: bold; font-style: italic;">Review Period</font>&#8221;).





                    [***]. Notwithstanding any provision to contrary set forth in this Agreement, Otsuka will [***]. Otsuka will provide Ionis a copy of any Otsuka Publication at the time of the submission or presentation thereof. Otsuka agrees to
                    determine the authorship of all Otsuka Publications in accordance with all applicable International Committee of Medical Journal Editors (ICMJE) guidelines. Otsuka will require its Affiliates and Sublicensees to comply with the
                    obligations of this <u>Section 12.5</u> (Publications) as if they were Otsuka, and Otsuka will be liable for any non-compliance of such Persons.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z0c16a66314fe453998eebc2aec324ce3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.5.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Ionis&#8217; Right to Publish</font>. Ionis will have the right to publicly present or publish any Clinical Trial data, non-clinical or preclinical data, or any associated results or conclusions generated
                    by or on behalf of Ionis pursuant to this Agreement (each such proposed presentation or publication, a &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Publication</font>&#8221;) [***]. If Ionis desires to publicly present or
                    publish an Ionis Publication in accordance with the foregoing sentence, then Ionis will provide Otsuka (including Otsuka&#8217;s Alliance Manager and all Otsuka members of the JSC) with a copy of such proposed Ionis Publication for review
                    during the applicable Review Period. [***]. Notwithstanding any provision to contrary set forth in this Agreement, Ionis will [***]. Ionis will provide Otsuka a copy of any Ionis Publication at the time of the submission or presentation
                    thereof. Ionis agrees to determine the authorship of all Ionis Publications in accordance with all applicable International Committee of Medical Journal Editors (ICMJE) guidelines. Ionis will require its Affiliates to comply with the
                    obligations of this <u>Section 12.5</u> (Publications) as if they were Ionis, and Ionis will be liable for any non-compliance of such Persons.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z5676c0e65fc943649af549a707418dae" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.5.3</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Subsequent Publications</font>. After any Otsuka Publication or Ionis Publication has been published or publicly presented in accordance with <u>Section 12.5.1</u> (Otsuka&#8217;s Right to Publish) or <u>Section





                      12.5.2</u> (Ionis&#8217; Right to Publish), as applicable, either Party may make subsequent publications or presentations of the content of such previously published Otsuka Publication or Ionis Publication without further approval or review
                    by the other Party; <font style="font-style: italic;">provided</font>, that such subsequent publication or presentation does not include any new data, information or conclusions, or present the content in a form or manner that
                    materially alters the conclusion or subject matter of the previous publication or public presentation.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zaa5459e446124907813007f20fe2ac34" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.6</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Publicity; Use of Names</font>.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z8f38edfa25384697944a6dcce6299751" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.6.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Press Release</font>. The Parties may issue a press release announcing this Agreement, on such date and time and in such form, in each case, as may be agreed by the Parties.<font style="font-weight: bold; font-style: italic;">&#160;</font>Other than such press release and the public disclosures permitted by this <u>Section 12.6.1</u> (Press Release) and <u>Section 12.4</u> (Authorized Disclosures), the Parties agree that the
                    portions of any other news release or other public announcement relating to this Agreement or the performance hereunder that would disclose information other than that already in the public domain will require prior review and approval
                    by both Parties (with such approval not to be unreasonably withheld, conditioned, or delayed). However, the Parties agree that after (a) a disclosure pursuant to this <u>Section 12.6</u> (Publicity; Use of Names) or <u>Section 12.4</u>
                    (Authorized Disclosures) or (b) the issuance of a press release (including the initial press release) or other public announcement pursuant to this <u>Section 12.6.1</u> (Press Release) that has been reviewed and approved by the other
                    Party, the disclosing Party may make subsequent public disclosures reiterating such information without having to obtain the other Party&#8217;s prior consent and approval so long as the information in such press release or other public
                    announcement remains true, correct, and such disclosure is consistent with prior disclosures approved by the other Party pursuant to this <u>Section 12.6</u> (Publicity; Use of Names) and which do not reveal non&#8209;public information
                    about the other Party. Similarly, after a Publication has been made available to the public, each Party may post such Publication or a link to it on its corporate website or social media platforms (or any website managed by such Party
                    in connection with a Clinical Trial for the Licensed Products, as appropriate) without the prior written consent of the other Party, so long as the information in such Publication remains true, correct, and the most current information
                    with respect to the subject matters set forth therein.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">65</font></div>
            <div style="page-break-after: always;" class="BRPFPageBreak">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="z7a56c23bc57449d49e8f40499e810b6c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.6.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Disclosures by Ionis</font>. Notwithstanding any provision to the contrary set forth in this Agreement, Ionis has the right to publicly disclose (in written, oral, or other form): (a) the achievement
                    of any Regulatory Milestone Event or Sales Milestone Event under this Agreement (including the timing of achievement of any such milestone event but without disclosing the amount of such milestone payment unless permitted pursuant to <u>Section





                      12.4.1(d)</u> (Permitted Circumstances)); (b) the commencement, completion, material data, or key results of any Clinical Trials for the Licensed Products conducted by or on behalf of Ionis; and (c) the achievement of Regulatory
                    Approval for any Licensed Product throughout the world; <font style="font-style: italic;">provided </font>that,<font style="font-style: italic;">&#160;</font>subject to <u>Section 12.4.1(d)</u> (Permitted Circumstances), [***].</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zcd7daa5f31a841998edf194d0b801e28" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">12.6.3</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Use of Names</font>. Each Party will have the right to use the other Party&#8217;s name and logo in presentations, its website, collateral materials, and corporate overviews to describe the collaboration
                    relationship, as well as in taglines of press releases issued pursuant to this <u>Section 12.6</u> (Publicity; Use of Names); <font style="font-style: italic;">provided </font>that neither Party will [***], and each Party will [***].
                    Except as permitted under this <u>Section 12.6</u> (Publicity; Use of Names) or with the prior express written permission of the other Party, neither Party will use the name, trademark, trade name, or logo of the other Party or its
                    Affiliates or their respective employees in any publicity, promotion, news release, or disclosure relating to this Agreement or its subject matter except as may be required by Applicable Law.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div>
            <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z3ca5a1668d944522b735010e4c8ce64c">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.7</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Acknowledgement</font>.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zb9be506fda194df4a7753b1ff6e6c448">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 39.6pt; vertical-align: top;">12.7.1</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>To the extent permitted under Applicable Law in the Otsuka Territory, Otsuka will acknowledge in any press release, public presentation, or publication regarding a Licensed Product Ionis&#8217; role in discovering and developing the
                      Licensed Products, that the Licensed Products are under license from Ionis, and [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z228eaec1466341a3bf72de7231f8d1b1">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 39.6pt; vertical-align: top;">12.7.2</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Otsuka agrees that it will acknowledge Ionis&#8217; role in the discovery of a Licensed Product in any scientific, medical, and other Licensed Product-related communications [***], by including the words &#8220;<font style="font-style: italic;">Discovered by Ionis</font>&#8221; or equivalent language (collectively, the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Attribution Language</font>&#8221;) in any such communications; <font style="font-style: italic;">provided,




                        however</font>, that [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
          </div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">66</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
          </div>
          <div style="text-align: center; font-weight: bold;">ARTICLE 13</div>
          <div style="text-align: center; font-weight: bold;">INDEMNIFICATION</div>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z32ae5968b720408fb2843da1e3881ed9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Indemnification by Ionis</font>. Ionis will indemnify, hold harmless, and defend Otsuka and its Affiliates and their respective directors, officers, employees, and agents (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Indemnitee</font>&#8221;) from and against any and all Third Party suits, claims, actions, or demands (&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Claims</font>&#8221;)
                    and all liabilities, expenses, or losses (including reasonable attorneys&#8217; fees, court costs, witness fees, damages, judgments, fines, and amounts paid in settlement) (&#8220;<font style="font-weight: bold; font-style: italic;">Losses</font>&#8221;)
                    arising therefrom to the extent that the applicable Third Party Claims and such Losses arise out of (a) a breach of this Agreement by Ionis, (b) the Exploitation of the Licensed Products by or on behalf of Ionis or any of its
                    Affiliates, licensees (not including Otsuka or its Affiliates, Sublicensees, or its Subcontractors), Sublicensees, or Subcontractors, or (c) the negligence or willful misconduct of any Ionis Indemnitee. Notwithstanding the foregoing,
                    Ionis will not have any obligation to indemnify Otsuka Indemnitees to the extent that any Losses arise out of any Third Party Claim for which Otsuka is responsible for indemnifying Ionis pursuant to <u>Section 13.2</u> (Indemnification
                    by Otsuka).</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z01812de300224e81ab770ad66610d789" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Indemnification by Otsuka</font>. Otsuka will indemnify, hold harmless, and defend Ionis and its Affiliates, and their respective directors, officers, employees, and agents (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Indemnitee</font>&#8221;) from and against any and all Third Party Claims and all Losses arising therefrom, to the extent that the applicable Third Party Claims and such Losses arise out
                    of (a) a breach of this Agreement by Otsuka, (b) the Exploitation of the Licensed Products by or on behalf of Otsuka or any of its Affiliates, Sublicensees, or Subcontractors, or (c) the negligence or willful misconduct of any Otsuka
                    Indemnitee<font style="color: rgb(0, 0, 0);">. </font>Notwithstanding any provision to the contrary set forth in this Agreement,<font style="color: rgb(0, 0, 0);"> Otsuka will not have any obligation to indemnify the Ionis Indemnitees
                      to the extent that any&#160;</font>Losses arise out of any Third Party Claim for which Ionis is responsible for indemnifying Otsuka pursuant to <u>Section 13.1</u> (Indemnification by Ionis).</div>
                </td>
              </tr>

          </table>
          <br>
          <table cellspacing="0" cellpadding="0" id="z0f77d6120b824c809bd56635344fef11" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.3</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Indemnification Procedure</font>. If either Party is seeking indemnification under <u>Section 13.1</u> (Indemnification by Ionis) or <u>Section 13.2</u> (Indemnification by Otsuka) (the &#8220;<font style="font-weight: bold; font-style: italic;">Indemnified Party</font>&#8221;), then it will inform the other Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Indemnifying Party</font>&#8221;) of the Third Party Claim giving rise
                    to such indemnification obligations within [***] after receiving written notice of the Third Party Claim (it being understood and agreed, however, that the failure or delay by an Indemnified Party to give such notice of a Third Party
                    Claim will not affect the Indemnifying Party&#8217;s indemnification obligations hereunder except to the extent the Indemnifying Party will have been actually prejudiced as a result of such failure or delay to give notice). The Indemnifying
                    Party will have the right to assume the defense of any such Third Party Claim for which it is obligated to indemnify the Indemnified Party. The Indemnified Party will cooperate with the Indemnifying Party and the Indemnifying Party&#8217;s
                    insurer as the Indemnifying Party may reasonably request, and at the Indemnifying Party&#8217;s cost and expense. The Indemnified Party will have the right to participate, with counsel of its choice, in the defense of any Third Party that has
                    been assumed by the Indemnifying Party, which participation will be at the Indemnified Party&#8217;s expense unless (a) the Indemnifying Party has agreed to pay such fees and expenses, or (b) the Indemnified Party has been advised by counsel
                    that there are actual or potential conflicting interests between the Indemnifying Party and the Indemnified Party, including situations in which there are one or more legal defenses available to the Indemnified Party that are different
                    from or additional to those available to the Indemnifying Party. Neither Party will have the obligation to indemnify the other Party in connection with any settlement made without the Indemnifying Party&#8217;s written consent, which consent
                    will not be unreasonably withheld, conditioned, or delayed. The Indemnifying Party will not admit any fault or negligence on the part of the Indemnified Party, or impose any obligation on, or otherwise adversely affect, the Indemnified
                    Party, without the Indemnified Party&#8217;s prior written consent, which consent will not be unreasonably withheld, conditioned, or delayed. If the Parties cannot agree as to the application of <u>Section 13.1 </u>(Indemnification by
                    Ionis) or <u>Section 13.2</u> (Indemnification by Otsuka) as to any Third Party Claim, then, pending resolution of the dispute pursuant to <u>Article 15</u> (Dispute Resolution; Governing Law), then the Parties may conduct separate
                    defenses of such Third Party Claims, with each Party retaining the right to claim indemnification from the other Party in accordance with <u>Section 13.1</u> (Indemnification by Ionis) or <u>Section 13.2</u> (Indemnification by
                    Otsuka), as applicable, upon resolution of the underlying Third Party Claim.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">67</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="z422baca345b54391a88ceb5876bad7ea" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.4</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Insurance</font>. Each Party will, at its own expense, procure and maintain insurance, including product liability insurance, adequate to cover its obligations hereunder and that is consistent with
                    normal business practices of prudent companies similarly situated at all times during which any Licensed Product is being clinically tested in human subjects or commercially distributed or sold by such Party pursuant to this Agreement.
                    It is understood that such insurance will not be construed to create a limit of either Party&#8217;s liability with respect to its indemnification obligations under this <u>Article 13</u> (Indemnification). Each Party will provide the other
                    Party with written evidence of such insurance upon request. Each Party will provide the other Party with [***].</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div style="text-align: center; font-weight: bold;">ARTICLE 14</div>
          <div style="text-align: center; font-weight: bold;">TERM AND TERMINATION</div>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z950e1b8278b4494bb63bd309d022b5aa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Term</font>. The term of this Agreement will begin on the Restatement Date and, unless earlier terminated in accordance with this <u>Article 14</u> (Term and Termination), will continue until Otsuka,
                    its Affiliates, and its Sublicensees are no longer Commercializing any Licensed Product in any country in the Otsuka Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Term</font>&#8221;).</div>
                </td>
              </tr>

          </table>
          <br>
          <table cellspacing="0" cellpadding="0" id="z463d06a7be114b20a37a327a2e1123ab" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Termination for Material Breach</font>.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z3d47b2ed4ac5478fa7902588848d5fff" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.2.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Material Breach</font>. If either Party believes in good faith that the other Party is in material breach of its obligations under this Agreement with respect to a given Region, then the non-breaching
                    Party may deliver notice of such breach to the other Party stating the cause and proposed remedy (&#8220;<font style="font-weight: bold; font-style: italic;">Breach Notification</font>&#8221;). For any breach alleged in any Breach Notification
                    arising from a failure to make a payment set forth in this Agreement, the allegedly breaching Party will have [***] from the receipt of the applicable Breach Notification to cure such breach. For all breaches other than a failure to
                    make a payment as set forth in this Agreement, the allegedly breaching Party will have [***] from the date of the Breach Notification to cure such breach. If the allegedly breaching Party fails to cure the applicable breach within the
                    applicable period set forth above, then the Party originally delivering the Breach Notification may terminate this Agreement with respect to the applicable Region effective on written notice of termination to such allegedly breaching
                    Party. For clarity, if the material breach relates to this Agreement as a whole, then the non-breaching Party will have the right to terminate this Agreement in its entirety in accordance with this <u>Section 14.2.1</u> (Material
                    Breach).</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zff3edaa0ca894f59b09fb043084c7771" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.2.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Disagreement as to Material Breach</font>. Notwithstanding <u>Section 14.2.1</u> (Material Breach), if the Parties, reasonably and in good faith, disagree as to whether there has been a material
                    breach of this Agreement, then: (a) the Party that disputes whether there has been a material breach may contest the allegation by referring such matter, within the cure period applicable to such alleged material breach, for resolution
                    in accordance with <u>Article 15</u> (Dispute Resolution; Governing Law); (b) the relevant cure period with respect to such alleged material breach will be tolled from the date on which the Party that disputes whether there has been a
                    material breach notifies the other Party of such dispute and through the resolution of such dispute in accordance with <u>Article 15</u> (Dispute Resolution; Governing Law); and (c) during the pendency of such dispute, all of the terms
                    and conditions of this Agreement will remain in effect and the Parties will continue to perform all of their respective obligations hereunder.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">68</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="z4c0f1ace28c648dab02705a1bc2c4ae5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.3</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Termination by Otsuka for Convenience</font>. At any time during the Term, Otsuka will have the right to terminate this Agreement (a) ***] or (b) [***].</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z29cfbfc128034c9dbee120b3207bcbea" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.4</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Discontinuation of Development and Commercialization</font>. If Otsuka and its Affiliates and Sublicensees have not conducted any material Development or Commercialization activities with respect to
                    the Licensed Products in any country in the Otsuka Territory for a continuous period of [***], and such discontinuation of activity is not: (a) by written agreement of the Parties,&#160;(b) due to [***], or (c) due to a Force Majeure,<font style="font-weight: bold; font-style: italic;">&#160;</font>then Ionis may, at its election, terminate this Agreement in its entirety upon [***] prior written notice to Otsuka. For purposes of this <u>Section 14.4</u> (Discontinuation of
                    Development and Commercialization), the use of reasonable efforts, to the extent possible, by Otsuka or its Affiliates or Sublicensees (as applicable) to resolve a Force Majeure, clinical hold or other action or inaction of a Regulatory
                    Authority, or any scientific or technical issues, Manufacturing or supply interruption or other material adverse event outside of Otsuka&#8217;s control for the Licensed Product will, in each case, be considered material Development or
                    Commercialization activities.</div>
                </td>
              </tr>

          </table>
          <div> <br>
          </div>
          <table cellspacing="0" cellpadding="0" id="z8e3538faf0ae420c9d83babb3c8bdb7d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.5</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Termination for Patent Challenge</font>. Except to the extent unenforceable under Applicable Law, Ionis may terminate this Agreement in its entirety upon [***] prior written notice of termination to
                    Otsuka if Otsuka or its Affiliates or Sublicensees (individually or in association with any Person) commences or assists a Third Party in commencing or conducting a Patent Challenge with respect to any Ionis Patent Right, <font style="font-style: italic;">provided</font> that, Ionis shall not have the right to terminate this Agreement on account of such Patent Challenge (a) if, within [***] after receipt by Otsuka of the written notice from Ionis as set
                    forth above in this <u>Section 14.5</u> (Termination for Patent Challenge), Otsuka or its Affiliate, as applicable, rescinds such Patent Challenge (or in the case of any ex-parte proceeding, multi-party proceeding, or other Patent
                    Challenge that Otsuka or such Affiliate does not have the power to unilaterally withdraw or cause to be withdrawn, Otsuka and its Affiliate, as applicable, knowingly ceases providing any direction to any Person with respect to such
                    Patent Challenge and, to the extent Otsuka or any of its Affiliates is a party to such Patent Challenge and to the extent permitted by the applicable tribunal, it withdraws from such Patent Challenge) and <font style="font-style: italic;">provided</font> that neither Otsuka nor any of its Affiliates thereafter continues such Patent Challenge or, knowingly provides any direction to any Person in respect of the same or (b) in the case of any Patent Challenge
                    commenced by a Sublicensee of Otsuka or its Affiliate, if Otsuka or its Affiliate, as applicable, terminates such Sublicensee&#8217;s sublicense under any Ionis Technology within [***] after receipt by Otsuka of the applicable written notice
                    from Ionis as set forth above in this <u>Section 14.5</u> (Termination for Patent Challenge). If Ionis has the right to terminate this Agreement in accordance with this <u>Section 14.5</u> (Termination for Patent Challenge) but such
                    termination is prohibited under Applicable Law, then in lieu of such termination, [***]. If Ionis [***], then [***]. Notwithstanding the foregoing, Ionis shall not have the right to terminate this Agreement pursuant to this <u>Section
                      14.5</u> (Termination for Patent Challenge) if Otsuka or any of its Affiliates or its or their Sublicensees commences a Patent Challenge (i) in a proceeding involving an Ionis Patent Right in which Otsuka or any of its Affiliates or
                    its or their Sublicensees has been compelled to participate in the proceeding by a court, patent office, or Third Party or (ii) that is necessary or reasonably required to assert a cross-claim or a counterclaim or to respond to a court
                    request or order or administrative law request or order, including asserting any defense or counterclaim in, or otherwise responding to, an action for infringement of intellectual property asserted, filed or threatened to be filed
                    against Otsuka or any of its Affiliates or its or their Sublicensees by Ionis or any of its Affiliates or its or their Sublicensees.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">69</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="zf13c2d0cd8d84c10998a328bc70ad68b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.6</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Termination for Insolvency</font>. Each Party will have the right to terminate this Agreement upon delivery of written notice to the other Party if (a) such other Party files in any court or agency
                    pursuant to any statute or regulation of any jurisdiction a petition in bankruptcy or insolvency or for reorganization or similar arrangement for the benefit of creditors or for the appointment of a receiver or trustee of such other
                    Party or its assets, (b) such other Party is served with an involuntary petition against it in any insolvency proceeding and such involuntary petition has not been stayed or dismissed within [***] of its filing, or (c) such other Party
                    makes an assignment of substantially all of its assets for the benefit of its creditors.</div>
                </td>
              </tr>

          </table>
          <br>
          <table cellspacing="0" cellpadding="0" id="zde5280fc47e44912894158a4fe96b76f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.7</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Rights in Bankruptcy</font>. The Parties intend to take advantage of the protections of Section 365(n) (or any successor provision) of the U.S. Bankruptcy Code or any analogous provisions in any other
                    country or jurisdiction to the maximum extent permitted by Applicable Law. All rights and licenses granted under or pursuant to this Agreement shall be deemed to be &#8220;intellectual property&#8221; for the purposes of Section 365(n) or any
                    analogous provisions in any other country or jurisdiction. The Parties shall retain and may fully exercise all of their rights and elections under the U.S. Bankruptcy Code or any analogous provisions in any other country or
                    jurisdiction, including the right to obtain the intellectual property from another entity. In the event of the commencement of a bankruptcy proceeding by or against either Party under the U.S. Bankruptcy Code or any analogous provisions
                    in any other country or jurisdiction, the Party that is not subject to such proceeding shall be entitled to a complete duplicate of (or complete access to, as appropriate) all such intellectual property (including all embodiments of
                    such intellectual property), which, if not already in the non-subject Party&#8217;s possession, shall be promptly delivered to it upon the non-subject Party&#8217;s written request (a) upon commencement of a bankruptcy proceeding, unless the Party
                    subject to such proceeding continues to perform all of its obligations under this Agreement, or (b) if not delivered pursuant to clause (a) above because the subject Party continues to perform, upon the rejection of this Agreement by or
                    on behalf of the subject Party. Unless and until the subject Party rejects this Agreement, the subject Party shall perform this Agreement or provide the intellectual property (including all embodiments of such intellectual property) to
                    the non-subject Party, and shall not interfere with the rights of the non-subject Party to such intellectual property, including the right to obtain the intellectual property from another entity.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zf127e345d7ab47e4b3d9346a37c0531f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.8</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Full Force and Effect During Notice Period</font>. This Agreement will remain in full force and effect until the expiration of the applicable termination notice period. For clarity, if Otsuka or any
                    of its Affiliates or Sublicensees achieve any Milestone Events during the termination notice period, then the corresponding Milestone Payment is accrued and Otsuka will remain responsible for the payment of such Milestone Payment even
                    if the due date of such Milestone Payment occurs after the effective date of the termination.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z40650bdc22b840bfb188c72b6a22d257" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.9</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Effects of Termination</font>. If this Agreement is terminated by either Party pursuant to <u>Section 14.2</u> (Termination for Material Breach) or <u>Section 14.6</u> (Termination for Insolvency),
                    by Otsuka pursuant to <u>Section 14.3</u> (Termination by Otsuka for Convenience), or by Ionis pursuant to <u>Section 14.4</u> (Discontinuation of Development and Commercialization), or <u>Section 14.5</u> (Termination for Patent
                    Challenge), then all rights in the Licensed Products in the Terminated Regions will revert to Ionis, and the following will apply with respect to the Licensed Products in the Terminated Regions:</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z9732c5191b71421c88858eb80fd3a253" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.9.1</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Termination of Licenses</font>. As of the effective date of termination of this Agreement, all rights licensed to Otsuka under <u>Section 2.1</u> (License Grants to Otsuka) or otherwise under this
                    Agreement (except for the licenses granted under <u>Section 2.4</u> (Collaboration Technology Enabling License)), in each case, will each terminate with respect to the Terminated Region, but each Party will retain its joint ownership
                    interests in the Joint Collaboration Technology.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">70</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="z3a168db062ef426da0c21c986322f863" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.9.2</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Reversion License</font>.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z170f41792cf3440481c151e3cd4dfc1c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(a)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">License Grant</font>. Ionis will have, and Otsuka hereby grants to Ionis, effective upon such termination, a worldwide, [***] license under any Patent Rights and Know-How Controlled by Otsuka as of
                    the effective date of such termination, other than any Otsuka Technology, that, in each case, are used by Otsuka or its Affiliates in the Exploitation of any Licensed Product in the Terminated Region(s) prior to or as of the effective
                    date of such termination solely to Exploit the Licensed Products in the Terminated Region(s) (the &#8220;<font style="font-weight: bold; font-style: italic;">Reversion License</font>&#8221;). Except as otherwise provided in <u>Section 14.9.8</u>
                    (Sell-Off), Otsuka will not have the right to Commercialize any Licensed Product in the Terminated Region(s) upon and following the effective date of termination of this Agreement with respect to such Terminated Region(s).</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z4d179c2e3ff04556b6ed126b9ab5a983" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(b)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Reversion Royalty</font>. Ionis will pay, on a Calendar Quarter basis during the applicable Royalty Term (defined <font style="font-style: italic;">mutatis mutandis</font> with respect to the
                    Reversion License except that, for clarity, references to the Ionis Patent Rights in such definition will instead refer to any Patent Rights licensed by Otsuka to Ionis under the Reversion License) a [***] royalty on Ionis&#8217; Net Sales
                    (defined <font style="font-style: italic;">mutatis mutandis</font> with respect to the Reversion License) of each Licensed Product in the Terminated Region(s). The provisions of <u>Section 9.3.4</u> (Royalty Payments and Reports)
                    through <u>Section 9.11</u> (Late Payments; Disputed Payments) will apply to such payment obligation <font style="font-style: italic;">mutatis mutandis. </font>Notwithstanding the foregoing, in no event will the total amount of the
                    reversion royalty payments under this <u>Section 14.9.2(b)</u> (Reversion Royalty) exceed [***].</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z7f585ac7b5f7456a9cce95a8eabb937d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.9.3</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Transition Services</font>.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z8773edd78fca4b65a61db9b05824a671" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(a)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Scope</font>. Ionis may request that Otsuka perform transition activities with respect to any Licensed Products in the Terminated Region(s) that are necessary to transition the responsibilities under
                    all Regulatory Approvals for the Licensed Products in the Terminated Region(s) and ongoing Clinical Trials in the Terminated Region(s) for Licensed Products to Ionis or its designee. If Ionis requests that Otsuka perform any such
                    transition activities, then the Parties will enter into a transition agreement containing a plan for Otsuka to perform the transition services listed in <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 14.9.3</u>
                    (Transition Services), to the extent applicable at the time of termination, and such other transition services that the Parties mutually agree to (such plan, the &#8220;<font style="font-weight: bold; font-style: italic;">Transition Plan</font>&#8221;
                    and such activities, the &#8220;<font style="font-weight: bold; font-style: italic;">Transition Services</font>&#8221;).</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zd438dd62c3c34874adb021d22e5e64e3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(b)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Transition Plan</font>. Ionis may elect to have Otsuka perform the Transition Services by providing written notice to Otsuka no later than [***] following the effective date of the termination in the
                    Terminated Region(s). If Ionis requests that Otsuka perform the Transition Services, then Ionis will propose a draft of the Transition Plan setting forth the Transition Services to be performed by Otsuka and the Parties will negotiate
                    and enter into the Transition Plan, which will be consistent with this <u>Section 14.9.3</u> (Transition Services) and will include, to the extent applicable, the services listed on <font style="font-variant: small-caps;"><u>Schedule</u></font><u>
                      14.9.3</u> (Transition Services), within [***] after such request. In addition, the Parties will, within [***] after such request, establish a transition committee consisting of at least each Party&#8217;s Alliance Managers, a
                    representative from each Party&#8217;s CMC group who was responsible for the Licensed Product prior to the termination in the Terminated Region(s), and up to two additional representatives from each Party who are from other relevant
                    functional groups to facilitate a smooth transition. While Otsuka is providing Transition Services, Otsuka and Ionis will mutually agree on talking points and a communication plan to customers, specialty pharmacies, physicians,
                    Regulatory Authorities, patient advocacy groups, and clinical study investigators, in each case, in the Terminated Region(s), and Otsuka will make all such communication to such entities in accordance with the mutually agreed talking
                    points.</div>
                </td>
              </tr>

          </table>
          <div> <br>
          </div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">71</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="z20cbb37d38c949a4a3c89ed71c789338" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(c)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Costs</font>. Ionis will pay Otsuka for [***]. In addition, Ionis will reimburse Otsuka for [***]. Otsuka will submit an invoice, together with supporting documentation of [***], to Ionis quarterly
                    for the foregoing costs incurred by or on behalf of Otsuka in such Calendar Quarter, and Ionis will pay the undisputed invoiced amounts within [***] after the date of such invoice (and will pay any disputed amounts within [***]
                    following resolution of the dispute and determination that such amounts are owed).</div>
                </td>
              </tr>

          </table>
          <br>
          <table cellspacing="0" cellpadding="0" id="z34a57d2b82a7456e95153fa811a68a62" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.9.4</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Return of Confidential Information</font>. Each Party will return or destroy (at the other Party&#8217;s election) all Confidential Information of the other Party to the extent relating to the Terminated
                    Region(s) in its possession upon termination of this Agreement in such Terminated Region(s) and, if applicable, the Receiving Party will provide a written confirmation of such destruction within [***] of such request. Notwithstanding
                    the foregoing or any provision to the contrary set forth in this Agreement: (a) the foregoing terms of this <u>Section 14.9.4</u> (Return of Confidential Information) will not apply to any Confidential Information that is necessary to
                    allow the Receiving Party to perform its obligations or exercise any of its rights that expressly survive the applicable termination of this Agreement in such Terminated Region(s), and the Receiving Party may retain one copy of such
                    Confidential Information for its legal archives; and (b) the Receiving Party will not be required to destroy electronic files containing such Confidential Information that are made in the ordinary course of its business information
                    back-up procedures pursuant to its electronic record retention and destruction practices that apply to its own general electronic files and information.</div>
                </td>
              </tr>

          </table>
          <br>
          <table cellspacing="0" cellpadding="0" id="zc6c5e1a510d145609c70894e7759c94d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.9.5</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Sublicenses</font>. If this Agreement is terminated prior to expiration, then Ionis shall grant to each Sublicensee of Otsuka with respect to one or more Terminated Regions, at each such Sublicensee&#8217;s
                    written request to Ionis within [***] of the effective date of termination in such Terminated Region(s), a direct license, <font style="font-style: italic;">provided</font> that such Sublicensee (a) is not then in default of its
                    sublicense agreement or this Agreement, (b) agrees in writing to comply with the terms of this Agreement to the extent applicable to the rights originally sublicensed to such Sublicensee by Otsuka, and (c) agrees to pay directly to
                    Ionis such Sublicensee&#8217;s payments under such sublicense agreement. The scope of such direct license shall be no less than the scope of the license granted herein and sublicensed to such Sublicensee, and Ionis shall have no obligation to
                    perform any task for such Sublicensee beyond the obligations owed to Otsuka hereunder. Each Sublicensee will be an intended Third Party beneficiary of this <u>Section 14.9.5</u> (Sublicenses) with the right to enforce the same against
                    Ionis.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z931c6a64f5374c0aa79140bda2400677" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.9.6</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Assignment</font>. To the extent requested by Ionis in writing following the date that a Party provides notice of termination of this Agreement in the Terminated Region(s), Otsuka will promptly (and
                    in any event no later than [***] after the effective date of termination in the Terminated Region(s) unless agreed otherwise in the Transition Plan or expressly specified otherwise below):</div>
                </td>
              </tr>

          </table>
          <br>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">72</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="zf74c658659284e7da1b693b1df1b70f8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(a)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>provide to Ionis for its review unredacted copies of all clinical trial agreements and distribution agreements with respect to one or more Terminated Regions (to the extent assignable, not cancelled, and solely related to the
                    Licensed Products), in each case, that are necessary or reasonably useful for the Exploitation of the Licensed Products in the Terminated Region(s), and, following such review, upon Ionis&#8217; written request within [***] after entering
                    into a Transition Plan or [***] after the effective date of termination in the Terminated Region(s) if Ionis does not elect to enter into a Transition Plan, assign and transfer to Ionis or its designee all of Otsuka&#8217;s rights, title, and
                    interests in and to any such agreements;</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z3ac5d18191e6491c9891e9d853e5bfdc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(b)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>assign to Ionis any Potential In-Licenses with respect to one or more Terminated Regions entered into by Otsuka pursuant to <u>Section 2.7.2</u> (Potential In-Licenses);</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z7dcd6277af4844da9ef43b9c8cfb2964" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(c)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>assign any agreements or arrangements with Third Party vendors (including distributors) with respect to one or more Terminated Regions solely related to the Licensed Products or, to the extent any such Third Party agreement or
                    arrangement is not assignable to Ionis, reasonably cooperate with Ionis to arrange to continue to provide such services for a reasonable time after termination of this Agreement in the Terminated Region(s) to facilitate the orderly
                    transition of all Commercialization and other activities then being performed by or on behalf of Otsuka or its Affiliates or Sublicensees for the Licensed Products in the Terminated Region(s) to Ionis or its designee;</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z763e0835da9b48e8bdab24977492c321" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(d)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>assign and transfer to Ionis or its designee, as of the effective date of termination in the Terminated Region(s), all of Otsuka&#8217;s rights, title, and interests in and to the Otsuka Product Trademarks in the Terminated Region(s) and
                    any domain names associated with the Otsuka Product Trademarks (to the extent that Otsuka or its Affiliates has any) in the Terminated Region(s) and promptly provide to Ionis all information necessary to maintain such domain names;</div>
                </td>
              </tr>

          </table>
          <br>
          <table cellspacing="0" cellpadding="0" id="zceb95d38525a4247b09de44df3d925b9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(e)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>assign and transfer to Ionis or its designee, as of the effective date of termination in the Terminated Region(s), all of Otsuka&#8217;s rights, title, and interests in and to any Product Materials in the Terminated Region(s) specifically
                    related to the Licensed Products,<font style="font-weight: bold; font-style: italic;">&#160;</font>and copyrights and any registrations for the foregoing (to the extent that Otsuka or its Affiliates has any); and</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zfde3485f6d874aa0b48b4520fb4cde23" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 75.6pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(f)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>within [***] after entering into a Transition Plan or [***] after the effective date of termination in the Terminated Region(s) if Ionis does not elect to enter into a Transition Plan, disclose to Ionis or its designee all documents,
                    records, and materials that embody any of the foregoing and that are Controlled by Otsuka.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div style="text-align: justify; margin-left: 75.6pt;">To the extent that any agreement or other asset described in this <u>Section 14.9.6 </u>(Assignment) is not assignable by Otsuka, then such agreement or other asset will not be assigned,
            and upon the request of Ionis, Otsuka will take such steps as may be necessary to allow Ionis to obtain and to enjoy the benefits of such agreement or other asset, in the form of a license or other right to the extent Otsuka has the right and
            ability to do so; <font style="font-style: italic;">provided</font> that such steps will not require Otsuka to [***] in order to obtain and enjoy such benefits. For clarity, Ionis will have the right to request that Otsuka take any or all of
            the foregoing actions in whole or in part, or with respect to all or any portion of the assets set forth in the foregoing provisions.</div>
          <div style="text-align: justify; margin-left: 75.6pt;"> <br>
          </div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">73</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="z30dca315b50c4dcebeff818d0c487c42" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.9.7</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Regulatory Submissions and Regulatory Approvals</font>. Otsuka will and hereby does, and will cause its Affiliates and Sublicensees to, (a) no later than [***] after the effective date of termination
                    of this Agreement in the Terminated Region(s), at Ionis&#8217; request either (i) assign and transfer to Ionis or its designee all of Otsuka&#8217;s rights, title, and interests in and to all Regulatory Submissions, Regulatory Approvals, and
                    Reimbursement Approvals in the Terminated Region(s) or (ii) solely with respect to any Terminated Region(s) in the Asia Territory, withdraw all Regulatory Submissions, Regulatory Approvals, and Reimbursement Approvals in such Terminated
                    Region(s), in each case ((i) or (ii)), solely for the Licensed Products in the Terminated Region(s) then Controlled by Otsuka or any of its Affiliates or Sublicensees (for any Sublicensees that do not become a direct licensee of Ionis
                    pursuant to <u>Section 14.9.5</u> (Sublicenses)), and (b) to the extent any assignment requested pursuant to clause (a) is delayed or is not permitted by the applicable Regulatory Authority, permit Ionis to cross-reference and rely
                    upon any such Regulatory Submissions, Regulatory Approvals, and Reimbursement Approvals filed by Otsuka or any of its Affiliates or Sublicensees (for any Sublicensees that do not become a direct licensee of Ionis pursuant to <u>Section
                      14.9.5</u> (Sublicenses)). Otsuka will execute and deliver, or will cause to be executed and delivered, to Ionis or its designee such endorsements, assignments, commitments, acknowledgements, and other documents as may be necessary to
                    effect the foregoing assignment, including submitting to each applicable Regulatory Authority or other Governmental Authority a letter or other necessary documentation (with copy to Ionis) notifying such Regulatory Authority or other
                    Governmental Authority of, or otherwise giving effect to, the transfer of ownership to Ionis of all such assigned Regulatory Submissions, Regulatory Approvals, and Reimbursement Approvals in the Terminated Region(s). In addition, upon
                    Ionis&#8217; written request, Otsuka will, [***] (other than in the event of termination of this Agreement by Otsuka pursuant to <u>Section 14.2</u> (Termination for Material Breach) or <u>Section 14.6</u> (Termination for Insolvency), in
                    which case Ionis shall [***]), provide to Ionis copies of all material related documentation, including material non-clinical, preclinical, and clinical data related to the Licensed Products in the Terminated Region(s) that are held by
                    or reasonably available to Otsuka or its Affiliates or Sublicensees (for any Sublicensees that do not become a direct licensee of Ionis pursuant to <u>Section 14.9.5</u> (Sublicenses)).</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z5fc398f4aed545ada5c8797703922d52" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.9.8</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Sell-Off</font>. If Otsuka is Commercializing any Licensed Product in any country in the Terminated Region(s) as of the applicable effective date of termination in such Terminated Region(s), then,
                    [***], either (a) Otsuka will appoint Ionis or its designee as its exclusive distributor of such Licensed Product in such country and grant Ionis or its designee the right to appoint sub-distributors, to the extent not prohibited by any
                    written agreement between Otsuka or any of its Affiliates and a Third Party or (b) Otsuka will have the continued right to sell the Licensed Products in the Terminated Region(s) from its inventory; <font style="font-style: italic;">provided</font>,
                    <font style="font-style: italic;">however</font>, that Otsuka&#8217;s obligations under this Agreement with respect to the Licensed Products that Otsuka sells in the Terminated Region(s), including the obligation to pay Royalties to Ionis
                    hereunder, will continue in full force and effect during such period. If Ionis elects to be appointed as the exclusive distributor pursuant to the foregoing clause (a), then the Parties will enter into a distribution agreement with
                    respect to such appointment and Ionis will use good faith efforts to distribute such Licensed Product in such country, or otherwise distribute such Licensed Product in such country, in accordance with the terms of the distribution
                    agreement.</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">74</font></div>
            <div class="BRPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" id="z733c2240853b413aa96d72d0a4baf6a7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.9.9</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Inventory</font>. [***].</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="zd0ddf51e54f945a3828e36c5abaf2e16" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.9.10</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Wind Down and Transition</font>. Otsuka will be responsible, [***] (other than in the event of termination of this Agreement by Otsuka pursuant to <u>Section 14.2</u> (Termination for Material
                    Breach) or <u>Section 14.6</u> (Termination for Insolvency), in which case Ionis shall [***]), for the wind-down of Otsuka&#8217;s and its Affiliates&#8217; and Sublicensees (for any Sublicensees that do not become a direct licensee of Ionis
                    pursuant to <u>Section 14.9.5</u> (Sublicenses)) activities with respect to the Licensed Products in the Terminated Region(s). Otsuka will, and will cause its Affiliates and such Sublicensees to, reasonably cooperate with Ionis to
                    facilitate orderly transition to Ionis or its designee of all Commercialization and other activities then being performed by or on behalf of Otsuka or its Affiliates for the Licensed Products in the Terminated Region(s).</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z5dcff876d18a4955bb48dbb73f106474" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.9.11</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Cost of Transition Activities</font>. Notwithstanding any provision to the contrary in this <u>Section 14.9</u> (Effects of Termination), but without limiting <u>Section 14.9.3(c)</u> (Costs), if
                    Otsuka terminates this Agreement pursuant to <u>Section 14.2</u> (Termination for Material Breach) or <u>Section 14.6</u> (Termination for Insolvency), Ionis will be responsible for, and will pay Otsuka, [***]. Otsuka will submit an
                    invoice, together with supporting documentation of [***], to Ionis quarterly for the foregoing costs incurred by or on behalf of Otsuka in such Calendar Quarter, and Ionis will pay the undisputed invoiced amounts within [***] after the
                    date of any such invoice (and will pay any disputed amounts within [***] following resolution of the dispute and determination that such amounts are owed).</div>
                </td>
              </tr>

          </table>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" id="z5320c062998142e0a1f44a150338888f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 39.6pt; vertical-align: top;">14.9.12</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Other Assistance; Further Assurances</font>. Otsuka will provide any other assistance reasonably requested by Ionis for the purpose of allowing Ionis or its designee to proceed expeditiously with the
                    Exploitation of the Licensed Products in the Terminated Region(s) for a period of [***] after the effective date of termination of this Agreement in such Terminated Region(s). Otsuka will execute all documents, and take all such further
                    actions as may be reasonably requested by Ionis in order to give effect to the requirements in this <u>Section 14.9</u> (Effects of Termination).</div>
                </td>
              </tr>

          </table>
          <br>
          <table cellspacing="0" cellpadding="0" id="zc630c216010f4e07bea3b64cb8a39a17" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.10</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-weight: bold;">Survival; Accrued Rights</font>. Expiration or termination of this Agreement with respect to Terminated Region(s) will not relieve the Parties of any liability that accrued hereunder prior to the
                    effective date of such expiration or termination in such Terminated Region(s) nor preclude either Party from pursuing all rights and remedies it may have hereunder or at law or in equity with respect to any breach of this Agreement, nor
                    prejudice either Party&#8217;s right to obtain performance of any obligation. Without limiting the foregoing, the following provisions of this Agreement will survive the expiration or termination of this Agreement with respect to Terminated
                    Region(s): <u>Section 2.2</u> (License Grant to Ionis); <u>Section 2.4</u> (Collaboration Technology Enabling License); <u>Section 4.6</u> (Development Records; Cooperation) (solely with respect to the obligation to maintain records
                    for at least [***] after the end of the Term or for such longer period as may be required by Applicable Law); <u>Article 9</u> (Payments) (solely with respect to amounts that accrued prior to the effective date of termination and, with
                    respect to <u>Section 9.5</u> (Financial Records and Audits), solely for [***] after the effective date of termination), <u>Section 10.1</u> (Inventions); <u>Section 11.5</u> (Disclaimer); <u>Section 11.6</u> (Limitation of
                    Liability); <u>Article 12</u> (Confidentiality, excluding <u>Section 12.5</u> (Publications)); <u>Article 13</u> (Indemnification); <u>Section 14.9</u> (Effects of Termination); this S<u>ection 14.10</u> (Survival; Accrued Rights);
                    <u>Article 15</u> (Dispute Resolution; Governing Law); <u>Article 16</u> (Miscellaneous); and <u>Appendix 1</u> (Definitions).</div>
                </td>
              </tr>

          </table>
          <div><br>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">75</font></div>
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <div style="text-align: center; font-weight: bold;">ARTICLE 15</div>
            <div style="text-align: center; font-weight: bold;">DISPUTE RESOLUTION; GOVERNING LAW</div>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zd73a37c1d84c4bbabd00ff41081f0aa5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.1</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Executive Officers; Disputes</font>. Each Party will ensure that an Executive Officer is designated for such Party at all times during the Term for dispute resolution purposes, and will promptly
                      notify the other Party of any change in its designated Executive Officer. In the event of a dispute, controversy or claim arising under, relating to, or in connection with this Agreement (except for disputes arising at the Executive
                      Committee, any JSC, or any other Subcommittee, which will be resolved in accordance with <u>Section </u><u>8.5</u> (Decision-Making) and <u>Section 8.6</u> (Resolution of Committee Disputes)) (a &#8220;<font style="font-weight: bold; font-style: italic;">Disputed Matter</font>&#8221;), then the Parties will refer such dispute to their respective Executive Officer, and such Executive Officers or designees will attempt in good faith to resolve such dispute. If the
                      Parties are unable to resolve any such dispute within [***] after both Parties have referred such dispute to their designated Executive Officers pursuant to this <u>Section 15.1</u> (Executive Officers; Disputes), then either Party
                      will have the right to pursue any and all remedies available at law or equity, as set forth in <u>Section 15.2</u> (Arbitration) or <u>Section 15.3</u> (Intellectual Property Disputes), as applicable.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z4f5fc7f62ba7435f87db87cc69a6891a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.2</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Arbitration</font>.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z3ca63f04e1e446c69aeb3c85351b00f1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 39.6pt; vertical-align: top;">15.2.1</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="color: rgb(0, 0, 0);">If the Parties are unable to resolve a Disputed Matter using the process described in <u>Section 15.1</u> (Executive Officers; Disputes) and <u>Section 15.3</u> (Intellectual Property Disputes)
                        does not apply, then a Party seeking further resolution of the Disputed Matter will submit the Disputed Matter to resolution by final and binding arbitration in accordance with this <u>Section 15.2</u> (Arbitration).</font></div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z3fe33add507d41afab39c6833e4b378e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 39.6pt; vertical-align: top;">15.2.2</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="color: rgb(0, 0, 0);">The seat, or legal place, of arbitration will be New York, New York. The arbitration will be administered by the International Chamber of Commerce pursuant to its Rules of Arbitration in effect at
                        the time of the arbitration, (the &#8220;</font><font style="font-weight: bold; font-style: italic; color: rgb(0, 0, 0);">Rules</font><font style="color: rgb(0, 0, 0);">&#8221;), except they may be modified as set forth herein, and applying the
                        substantive law specified in <u>Section 15.5</u> (Governing Law; English Language). The language of the arbitration will be English.</font></div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zec9a0c35ccec49d5a69e26688a6cac6b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 39.6pt; vertical-align: top;">15.2.3</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="color: rgb(0, 0, 0);">Unless a Party elects for application of the ICC&#8217;s Expedited Procedure Rules pursuant to <u>Section 15.2.4</u> (Arbitration) or the Expedited Procedure Rules otherwise apply because of the amount
                        in dispute, the arbitration will be conducted by a tribunal of three arbitrators. The claimant will nominate an arbitrator in its request for arbitration; the respondent will nominate an arbitrator within [</font>***<font style="color: rgb(0, 0, 0);">] of receipt of the request for arbitration; and the two-party nominated arbitrators will nominate the third, who will serve as chair of the tribunal, within [</font>***<font style="color: rgb(0, 0, 0);">]
                        of the second arbitrator&#8217;s appointment. If any of the three arbitrators are not nominated within the time prescribed above, then the ICC will appoint the arbitrator(s). Within [</font>***<font style="color: rgb(0, 0, 0);">] of the
                        commencement of arbitration, the Parties will attempt in good faith to reach agreement upon and thereafter follow procedures directed at assuring that the arbitration will be concluded and the award rendered within no more than [</font>***<font style="color: rgb(0, 0, 0);">] from the date the ICC Secretariat transmits the file to the arbitral tribunal. Failing such agreement, the arbitral tribunal will design and the Parties will follow procedures directed at meeting such
                        a time schedule. Each arbitrator must have at least [</font>***<font style="color: rgb(0, 0, 0);">] of business or legal experience in the pharmaceutical industry. An arbitrator will be deemed to meet these qualifications unless a
                        Party objects within [</font>***<font style="color: rgb(0, 0, 0);">] after the arbitrator is nominated.</font></div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">76</font></div>
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="za11e175380eb4ed1b70768d34daada32" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 39.6pt; vertical-align: top;">15.2.4</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="color: rgb(0, 0, 0);">Notwithstanding <u>Section 15.2.3</u> (Arbitration), if the Disputed Matter involves the dispute of a Breach Notification for any default other than a determination of an alleged failure to use
                        Commercially Reasonable Efforts to Develop or Commercialize the Licensed Product, the non-breaching Party may elect on notice to the breaching Party to apply the ICC Expedited Procedure Rules to the arbitration and, if such election
                        is made, the number of arbitrators will be one and the period for the rendering of the final award will be [</font>***<font style="color: rgb(0, 0, 0);">] from the date of the case management conference.</font></div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z26415b46736b4a508f82c7cf40401716" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 39.6pt; vertical-align: top;">15.2.5</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div style="color: rgb(0, 0, 0);">The Parties agree that any dispute concerning the propriety of the commencement of the arbitration or the scope and applicability of the agreement to arbitrate will be determined by the arbitrator(s).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zae8760fa8c07486b824fff9cb6e2f391" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 39.6pt; vertical-align: top;">15.2.6</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="color: rgb(0, 0, 0);">No tribunal of arbitrators will have the power to award damages excluded pursuant to <u>Section 11.6</u> (Limitation of Liability).</font></div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zfc626ffb87a741c68dbc5a97604208b5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 39.6pt; vertical-align: top;">15.2.7</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div style="color: rgb(0, 0, 0);">Article 38 of the Rules will apply with respect to the costs of the arbitration.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zc110291c1f6b44fb8a7d971548e87a67" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 39.6pt; vertical-align: top;">15.2.8</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div style="color: rgb(0, 0, 0);">Except as may be required by Applicable Law, neither a Party nor any arbitrator may disclose the existence, content, or results of any arbitration hereunder without the prior written consent of both
                      Parties, unless to protect or pursue a legal right. The arbitral award will be final and binding on the Parties and the Parties will carry out the award without delay. Judgment on the award so rendered may be entered in any court of
                      competent jurisdiction. No award or procedural order made in the arbitration shall be published.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze642c91840fa4e0da79fdb502b214246" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.3</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Intellectual Property Disputes</font>. Notwithstanding any provision to the contrary set forth in this Agreement, if a dispute arises under this Agreement with respect to the validity, scope,
                      enforceability, or ownership of any Patent Right or other intellectual property rights, and such dispute is not resolved in accordance with <u>Section 15.1</u> (Executive Officers; Disputes), then such dispute will be submitted to a
                      court of competent jurisdiction in the jurisdiction in which such Patent Right or other intellectual property right was granted or arose.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z8cedcdfd2f4142e9aa49e6cb64926159" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.4</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Equitable Remedies</font>. Notwithstanding any provision to the contrary set forth in this Agreement, the Parties each stipulate and agree that (a) the other Party&#8217;s Confidential Information
                      includes highly sensitive trade secret information such that a breach of <u>Article 12</u> (Confidentiality) by a Party will cause irrevocable harm for which monetary damages would not provide a sufficient remedy; and (b) in such
                      case of such breach of <u>Article 12</u> (Confidentiality), the non-breaching Party will be entitled to seek equitable relief, including specific performance, temporary or permanent restraining orders, preliminary injunction,
                      permanent injunction, or other equitable relief without the posting of any bond or other security. In addition, and notwithstanding any provision to the contrary set forth in this Agreement, in the event of any other actual or
                      threatened breach hereunder, the aggrieved Party may seek interim equitable relief (including temporary restraining orders, or other provisional equitable relief) from any court of competent jurisdiction without first submitting to
                      the dispute resolution procedures set forth in <u>Article 15</u> (Dispute Resolution; Governing Law) and shall retain that right after the appointment of the arbitrator(s).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zd11e1f9489374e529bee3da8bff7530b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.5</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Governing Law; English Language</font>. This Agreement and all amendments, modifications, alterations, or supplements hereto, and the rights of the Parties, will be construed under and governed by
                      the laws of the State of New York, United States, exclusive of its conflicts of laws principles. This Agreement has been prepared in the English language and the English language will control its interpretation. All consents, notices,
                      reports, and other written documents to be delivered or provided by a Party under this Agreement will be in the English language, and in the event of any conflict between the provisions of any document and the English language
                      translation thereof, the terms of the English language translation will control.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">77</font></div>
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <div style="text-align: center; font-weight: bold;">ARTICLE 16</div>
            <div style="text-align: center; font-weight: bold;">MISCELLANEOUS</div>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zc48b433c89074ba287126c6bafc25810" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.1</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Assignment</font>. This Agreement may not be assigned or otherwise transferred, nor may any right or obligation hereunder be assigned or transferred, by either Party without the prior written
                      consent of the other Party. Notwithstanding the foregoing, (a) Ionis may assign its rights to receive payments under this Agreement to one or more Persons (including as part of a royalty monetization transaction) (a &#8220;<font style="font-weight: bold; font-style: italic;">Payment Assignment</font>&#8221;) without consent of Otsuka; <font style="font-style: italic;">provided</font> that Ionis shall give prompt written notice to Otsuka upon making a Payment
                      Assignment, and any assignee of a Payment Assignment shall not have any rights, including any audit rights, hereunder (other than the right to receive payments under this Agreement) unless Otsuka provides express prior written
                      consent, which Otsuka may grant or withhold in its discretion,<font style="font-weight: bold; font-style: italic;">&#160;</font>and (b) either Party may, without consent of the other Party, assign this Agreement and its rights and
                      obligations hereunder (i) in whole or in part to an Affiliate of such Party (for so long as such Affiliate remains an Affiliate), or (ii) in whole to its successor-in-interest in connection with the sale of all or substantially all of
                      its assets, whether in a merger, acquisition, or similar transaction or series of related transactions. If there is an assignment pursuant to the foregoing clauses (b)(i) or (b)(ii), then such assignment will only be effective if the
                      Person to whom this Agreement is assigned agrees in writing to assume all of the assigning Party&#8217;s obligations under this Agreement and the assigning Party provides written notice of such assignment to the non-assigning Party within
                      [***] after the effective date of such assignment. Any attempted assignment of this Agreement in violation of this <u>Section 16.1</u> (Assignment) will be null, void, and of no legal effect. Any permitted assignee will assume all
                      assigned obligations of its assignor under this Agreement. This Agreement will be binding on and will inure to the benefit of the permitted successors and assigns of the Parties.</div>
                  </td>
                </tr>

            </table>
            <br>
            <table cellspacing="0" cellpadding="0" id="z2c82516ae1a94d989c823a94b210530d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.2</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Entire Agreement; Amendment</font>.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z569b4a5ddb6446879ba4e97f5290d6f5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 39.6pt; vertical-align: top;">16.2.1</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>This Agreement and the Ancillary Agreements, together with all exhibits and schedules attached hereto, is in effect from and after the Restatement Date. This Agreement constitutes the entire agreement between the Parties with
                      respect to the subject matter hereof, and supersedes and merges all prior and contemporaneous negotiations, representations, and understandings regarding the same <font style="font-style: italic;">except</font>, with respect to the
                      Original Agreement, as set forth in <u>Section 16.2.2</u> (Entire Agreement; Amendment) (including that certain mutual confidential disclosure agreement between the Parties dated [***] (&#8220;<font style="font-weight: bold; font-style: italic;">Confidential Disclosure Agreement</font>&#8221;)). All information shared by the Parties pursuant to the Confidential Disclosure Agreement and the Original Agreement will be Confidential Information under this Agreement from and
                      after the Restatement Date, and the use and disclosure thereof will be governed by <u>Article 12</u> (Confidentiality). This Agreement may not be modified or amended, except by another agreement in writing executed by duly authorized
                      signatories of each Party.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z562ac02028d64fe3ad243a8c4188599b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 39.6pt; vertical-align: top;">16.2.2</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>The Original Agreement is amended and restated in its entirety and superseded as of the Restatement Date by this Agreement; <font style="font-style: italic;">provided</font> that such amendment and restatement of the Original
                      Agreement does not relieve the Parties of any liability that accrued under the Original Agreement prior to the Restatement Date nor preclude either Party from pursuing all rights and remedies it may have hereunder or at law or in
                      equity with respect to any breach of the Original Agreement, nor prejudice either Party&#8217;s right to obtain performance of any obligation that was due during the Original Agreement Term. Notwithstanding any provision to the contrary in
                      the Original Agreement, including <u>Section 14.10</u> (Survival; Accrued Rights), the following provisions of the Original Agreement will survive the amendment and restatement of the Original Agreement: <u>Section 4.6</u>
                      (Development Records; Cooperation) (solely with respect to the obligation to maintain records for at least three years after the end of the Original Agreement Term or for such longer period as may be required by Applicable Law); <u>Article



                        9 </u>(Payments) (solely with respect to amounts that accrued prior to the Restatement Date and, with respect to <u>Section 9.5</u> (Financial Records and Audits), solely for 36 months after the Restatement Date); <u>Section 11.5</u>
                      (Disclaimer); <u>Section 11.6</u> (Limitation of Liability); <u>Article 13</u> (Indemnification); <u>Article 15 </u>(Dispute Resolution; Governing Law); <u>Article 16</u> (Miscellaneous) (solely to extent applicable to other
                      surviving provisions); and <u>Appendix 1</u> (Definitions) (solely to the extent applicable to other surviving provisions).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">78</font></div>
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="zf1549c3743814549a4971f7e15d8e1ee" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.3</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">No Strict Construction; Interpretation</font>. This Agreement has been prepared jointly and will not be strictly construed against either Party. Ambiguities, if any, in this Agreement will not be
                      construed against any Party, irrespective of which Party may be deemed to have authored the ambiguous provision. Except where the context expressly requires otherwise, (a) whenever any provision of this Agreement uses the term
                      &#8220;including&#8221; (or &#8220;includes&#8221;), such term will be deemed to mean &#8220;including without limitation&#8221; and &#8220;including but not limited to&#8221; (or &#8220;includes without limitations&#8221; and &#8220;includes but is not limited to&#8221;) regardless of whether the words
                      &#8220;without limitation&#8221; or &#8220;but not limited to&#8221; actually follow the term &#8220;including&#8221; (or &#8220;includes&#8221;); (b) &#8220;herein,&#8221; &#8220;hereby,&#8221; &#8220;hereunder,&#8221; &#8220;hereof,&#8221; and other equivalent words will refer to this Agreement in its entirety and not solely
                      to the particular portion of this Agreement in which any such word is used; (c) all definitions set forth herein will be deemed applicable whether the words defined are used herein in the singular or the plural; (d) wherever used
                      herein, any pronoun or pronouns will be deemed to include both the singular and plural and to cover all genders; (e)&#160; the schedules and exhibits to this Agreement, and the terms and conditions incorporated in such schedules and
                      exhibits will be deemed integral parts of this Agreement and all references in this Agreement to this Agreement will encompass such schedules and exhibits and the terms and conditions incorporated in such schedules and exhibits; <font style="font-style: italic;">provided</font> that if there is a conflict between the terms and conditions of this Agreement and any terms and conditions set forth in the schedules, or exhibits, then the terms of this Agreement will
                      control; (f) in the event of any conflict between the terms and conditions of this Agreement and any terms and conditions that may be set forth on any order, invoice, or verbal agreement by the Parties pursuant to this Agreement, the
                      terms and conditions of this Agreement will govern; (g) unless otherwise provided, all references to Sections, Articles, and Schedules in this Agreement are to Sections, Articles, and Schedules of and to this Agreement; (h) any
                      reference to any federal, national, state, local, or foreign statute or law will be deemed to also refer to all rules and regulations promulgated thereunder, and any reference to any law, rule, or regulation will be deemed to include
                      the then&#8209;current amendments thereto or any replacement or successor law, rule, or regulation thereof; (i) wherever used, the word &#8220;shall&#8221; and the word &#8220;will&#8221; are each understood to be imperative or mandatory in nature and are
                      interchangeable with one another; (j) the term &#8220;or&#8221; will be interpreted in the inclusive sense commonly associated with the term &#8220;and/or&#8221;; (k) references to a particular Person include such Person&#8217;s successors and assigns to the
                      extent not prohibited by this Agreement; (l) the section headings and captions used herein are inserted for convenience of reference only and will not be construed to create obligations, benefits, or limitations; (m) any definition of
                      or reference to any agreement, instrument, or other document herein will be construed as referring to such agreement, instrument, or other document as from time to time amended, supplemented, or otherwise modified (subject to any
                      restrictions on such amendments, supplements, or modifications set forth herein); (n) the word &#8220;notice&#8221; means notice in writing (whether or not specifically stated) and will include notices, consents, approvals, and other written
                      communications contemplated under this Agreement; and (o) provisions that require that a Party, the Parties, or any committee hereunder &#8220;agree,&#8221; &#8220;consent,&#8221; or &#8220;approve&#8221; or the like will require that such agreement, consent, or
                      approval be specific and in writing, whether by written agreement, letter, approved minutes, or otherwise (but excluding email and instant messaging).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">79</font></div>
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="z9ef32549e357487ea8964da2d2c3cd1d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.4</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Severability</font>. If any provision of this Agreement is declared invalid by a court of last resort or by any court or other governmental body the decision of which an appeal is not taken within
                      the time provided by law, then and in such event, this Agreement will be deemed to have been terminated only as to the portion thereof that relates to the provision invalidated by that decision and only in the relevant jurisdiction,
                      but this Agreement will remain in force, in all other respects and all other jurisdictions; <font style="font-style: italic;">provided, however</font>, that if the provision so invalidated is essential to this Agreement as a whole,
                      then the Parties will negotiate in good faith to amend the terms hereof as nearly as practical to carry out the original intent of the Parties, and, failing such amendment, either Party may submit the matter for resolution pursuant to
                      <u>Article 15</u><font style="color: rgb(0, 0, 0);">&#160;</font>(Dispute Resolution; Governing Law).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z04ce3ada799e4dd980438e54287aef29" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.5</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Force Majeure</font>. Neither Party will be held liable or responsible to the other Party nor be deemed to be in default under, or in breach of any provision of, this Agreement for failure or delay
                      in fulfilling or performing any obligation of this Agreement when such failure or delay is due to Force Majeure. For purposes of this Agreement, &#8220;<font style="font-weight: bold; font-style: italic;">Force Majeure</font>&#8221; is defined as
                      any cause beyond the control of the affected Party and without the fault or negligence of such Party, which may include acts of God; material changes in Applicable Law; war; civil commotion; destruction of production facilities or
                      materials by fire, flood, earthquake, explosion, or storm; labor disturbances; epidemic; pandemic; quarantine; and failure of public utilities or common carriers. Notwithstanding the foregoing, a Party will not be excused from making
                      payments owed hereunder due to any such Force Majeure circumstances affecting such Party. The Party affected by Force Majeure will immediately notify the other Party of such inability and of the period for which such inability is
                      expected to continue. The Party giving such notice will thereupon be excused from such of its obligations under this Agreement as it is thereby disabled from performing for so long as it is so disabled for up to [***], after which
                      time the Parties will promptly meet to discuss in good faith how to best proceed in a manner that maintains and abides by this Agreement. To the extent possible, each Party will use reasonable efforts to minimize the duration of any
                      Force Majeure.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z8cd01a99ba1a44d8bf342398d50ffc56" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.6</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Notices</font>. All notices that are required or permitted hereunder will be in writing and sufficient if delivered by internationally recognized overnight courier or sent by registered or certified
                      mail, postage prepaid, return receipt requested, and in each case, addressed as follows (with a courtesy copy sent by email, which will not constitute notice):</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div style="text-align: justify; margin-left: 50.4pt;">If to Ionis:</div>
            <div>&#160;</div>
            <div style="margin-left: 72pt;">Ionis Pharmaceuticals, Inc.</div>
            <div style="margin-left: 72pt;">2855 Gazelle Court </div>
            <div style="margin-left: 72pt;">Carlsbad, CA 92010</div>
            <div style="margin-left: 72pt;">Attention: Chief Business Officer</div>
            <div>&#160;</div>
            <div style="text-align: justify; margin-left: 50.4pt; font-style: italic;">With a copy (which will not constitute notice for purposes of this Agreement) to:</div>
            <div>&#160;</div>
            <div style="margin-left: 72pt;">[***]</div>
            <div style="margin-left: 72pt;">Attention: General Counsel</div>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">80</font></div>
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
            </div>
            <div style="text-align: justify; margin-left: 50.4pt;">If to Otsuka:</div>
            <div>&#160;</div>
            <div style="margin-left: 72pt;">Otsuka Pharmaceutical Co., Ltd.</div>
            <div style="margin-left: 72pt;">Shinagawa Grand Central Tower</div>
            <div style="margin-left: 72pt;">2-16-4 Konan, Minato-ku</div>
            <div style="margin-left: 72pt;">Tokyo, 108-8242 Japan</div>
            <div style="margin-left: 72pt;">Attn:&#160; Director, Global Business Development</div>
            <div style="margin-left: 72pt;">Email:&#160; [***]</div>
            <div><br>
            </div>
            <div style="text-align: justify; margin-left: 50.4pt;"><font style="font-style: italic;">With a copy (which will not constitute notice for purposes of this Agreement) to</font>:</div>
            <div>&#160;</div>
            <div style="margin-left: 72pt;">Otsuka Pharmaceutical Co., Ltd.</div>
            <div style="margin-left: 72pt;">Shinagawa Grand Central Tower</div>
            <div style="margin-left: 72pt;">2-16-4 Konan, Minato-ku</div>
            <div style="margin-left: 72pt;">Tokyo, 108-8242 Japan</div>
            <div style="margin-left: 72pt;">Attn:&#160; Director, Legal Affairs Department</div>
            <div style="margin-left: 72pt;">Email:&#160; [***]</div>
            <div><br>
            </div>
            <div style="margin-left: 72pt;">Otsuka Pharmaceutical Europe Ltd.</div>
            <div style="margin-left: 72pt;">2 Windsor Dials, Arthur Road,</div>
            <div style="margin-left: 72pt;">Windsor, SL4 1RS, United Kingdom</div>
            <div style="margin-left: 72pt;">Attn: General Counsel</div>
            <div style="margin-left: 72pt;">Email: [***]</div>
            <div><br>
            </div>
            <div style="text-align: justify; margin-left: 72pt;">or to such other address as the Party to whom notice is to be given may have furnished to the other Party in writing in accordance herewith. Any such notice will be deemed to have been given:
              (a) on the Business Day after dispatch if sent by internationally recognized overnight courier; or (b) on the fifth Business Day after dispatch if sent by registered or certified mail, postage prepaid, return receipt requested.</div>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z9914099ba6f44fcd8fc2cb6bc29288d4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.7</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Further Assurances</font>. The Parties agree to reasonably cooperate with each other in connection with any actions required to be taken as part of their respective obligations under this Agreement,
                      and will (a) furnish to each other such further information; (b) execute and deliver to each other such other documents; and (c) do such other acts and things (including working collaboratively to correct any clerical, typographical,
                      or other similar errors in this Agreement), all as the other Party may reasonably request for the purpose of carrying out the intent of this Agreement.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zd2d2e38256bd4bb08b4087ed2315bbfe" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.8</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Performance by Affiliates</font>. Notwithstanding any provision to the contrary set forth in this Agreement, either Party will have the right to perform any or all of its obligations and exercise
                      any or all of its rights under this Agreement through any Affiliate. Each Party hereby guarantees the performance by its Affiliates of such Party&#8217;s obligations under this Agreement and will cause its Affiliates to comply with the
                      provisions of this Agreement in connection with such performance.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z13efc4b6b1664e46b9f0e88b564d5901" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.9</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Agency</font>. Neither Party is, nor will be deemed to be an employee, agent, or representative of the other Party for any purpose. Each Party is an independent contractor, not an employee or
                      partner of the other Party. Neither Party will have the authority to speak for, represent, or obligate the other Party in any way without prior written authority from the other Party.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">81</font></div>
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="z13f88c27f23146cdbc483427eb896477" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.10</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Binding Effect; No Third-Party Beneficiaries or Obligors</font>. As of the Restatement Date, this Agreement will be binding upon and inure to the benefit of the Parties and their respective
                      permitted successors and assigns. Except as set forth in <u>Article 13</u> (Indemnification), no Person other than Ionis, Otsuka, and their respective permitted successors and assigns hereunder will be deemed an intended beneficiary
                      hereunder, nor have any right to enforce any obligation of any Party to this Agreement, nor will any Person other than Ionis and Otsuka and their respective permitted successors and assigns have any obligations to any Party under this
                      Agreement.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z3e51f336f4874949bd339a02a99aff5a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.11</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">No Waiver</font>. Any omission or delay by either Party at any time to enforce any right or remedy reserved to it, or to require performance of any of the terms, covenants, or provisions hereof, by
                      the other Party, will not constitute a waiver of such Party&#8217;s rights to the future enforcement of its rights under this Agreement. Any waiver by a Party of a particular breach or default by the other Party will not operate or be
                      construed as a waiver of any subsequent breach or default by the other Party.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zb6386c532c74415c84498508e86d85d0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.12</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Cumulative Remedies</font>. No remedy referred to in this Agreement, including termination of this Agreement, is intended to be exclusive, but each will be cumulative and in addition to any other
                      remedy referred to in this Agreement or otherwise available under law.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z2bd896ccff4c46ed8604abd8a5488444" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.13</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">Counterparts</font>. This Agreement may be executed in one or more counterparts, all of which taken together will be regarded as one and the same instrument. Each Party may execute this Agreement in
                      Adobe&#8482; Portable Document Format (PDF) sent by electronic mail. PDF signatures of authorized signatories of the Parties will be deemed to be original signatures, will be valid and binding upon the Parties, and, upon delivery, will
                      constitute due execution of this Agreement.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div style="text-align: center; font-style: italic;">[Remainder of page intentionally left blank; Signature page follows.]</div>
            <div style="text-align: center; font-style: italic;"> <br>
            </div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">82</font></div>
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
            </div>
            <div style="text-align: justify; text-indent: 45pt;">
              <div style="font-style: italic; font-weight: bold; text-indent: 9pt;">CONFIDENTIAL</div>
              <div><font style="font-weight: bold;"> <br>
                </font></div>
              <div> <font style="font-weight: bold;">IN WITNESS WHEREOF,</font> the Parties have executed this Agreement through their duly authorized representatives to be effective as of the Restatement Date.</div>
            </div>
            <div>&#160;</div>
            <div>
              <table cellspacing="0" cellpadding="0" border="0" id="z212e82b1a97a4837a3045b7c8152d330" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

                  <tr>
                    <td style="vertical-align: top;" colspan="2">
                      <div style="text-align: justify; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
                    </td>
                    <td style="width: 10%; vertical-align: top;">&#160;</td>
                    <td style="vertical-align: top;" colspan="2">
                      <div style="text-align: justify; color: #000000; font-variant: small-caps; font-weight: bold;">Otsuka Pharmaceutical Co., Ltd.</div>
                    </td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                    <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top; padding-bottom: 2px; width: 3%;" rowspan="1">&#160;By:</td>
                    <td style="vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); width: 42%;" rowspan="1">
                      <div style="margin-left: 9pt"><font style="font-style: italic;">/s/ Brett Monia, PhD</font></div>
                    </td>
                    <td style="width: 10%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
                    <td style="vertical-align: top; padding-bottom: 2px; width: 3%;" rowspan="1">&#160;By: </td>
                    <td style="vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); width: 42%;" rowspan="1">
                      <div style="margin-left: 9pt"><font style="font-style: italic;">/s/ Makoto Inoue</font></div>
                    </td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                    <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top;" colspan="2">
                      <div style="text-align: justify; color: #000000;">Name:&#160; Brett Monia, PhD</div>
                    </td>
                    <td style="width: 10%; vertical-align: top;">&#160;</td>
                    <td style="vertical-align: top;" colspan="2">
                      <div style="text-align: justify; color: #000000;">Name: Makoto Inoue</div>
                    </td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                    <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top;" colspan="2">
                      <div style="text-align: justify; color: #000000;">Title:&#160; Chief Executive Officer</div>
                    </td>
                    <td style="width: 10%; vertical-align: top;">&#160;</td>
                    <td style="vertical-align: top;" colspan="2">
                      <div style="text-align: justify; color: #000000;">Title:&#160; President and Representative Director</div>
                    </td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                    <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top;" colspan="2"><br>
                    </td>
                    <td style="width: 10%; vertical-align: top;">&#160;</td>
                    <td style="vertical-align: top;" colspan="2"><font style="font-weight: bold;">Otsuka Pharmaceutical Co., Ltd.</font></td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                    <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top; padding-bottom: 2px;" colspan="2" rowspan="1">&#160;</td>
                    <td style="width: 10%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
                    <td style="vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;By:</td>
                    <td style="vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">
                      <div style="margin-left: 9pt"><font style="font-style: italic;">/s/ Takeshi Watanabe</font></div>
                    </td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                    <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top;" colspan="2">&#160;</td>
                    <td style="width: 10%; vertical-align: top;">&#160;</td>
                    <td style="vertical-align: top;" colspan="2">
                      <div style="text-align: justify; color: #000000;">Name:&#160; Takeshi Watanabe, PhD, MBA</div>
                    </td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                    <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
                    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
                  </tr>
                  <tr>
                    <td style="vertical-align: top;" colspan="2">&#160;</td>
                    <td style="width: 10%; vertical-align: top;">&#160;</td>
                    <td style="vertical-align: top;" colspan="2">
                      <div style="text-align: justify; color: #000000;">Title:&#160; VP, Global Head of Business Development</div>
                    </td>
                  </tr>

              </table>
              <div> <br>
              </div>
              <div>
                <div style="text-align: center;">[Signature Page to Amended and Restated License Agreement]</div>
                <div style="text-align: center;"> <br>
                </div>
              </div>
            </div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
            </div>
            <font style="font-style: italic; font-weight: bold;">CONFIDENTIAL</font>
            <div style="text-align: center; font-weight: bold;"><u>Appendix 1</u></div>
            <div>&#160;</div>
            <div style="text-align: center; font-weight: bold;">Definitions</div>
            <div>&#160;</div>
            <div style="text-align: justify; text-indent: 36pt;">For purposes of this Agreement, whether used in the singular or plural, the following terms will have the meanings set forth below:</div>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zc3c565a65ee046fab242cef17ce5fbd1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.1</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Accounting Standards</font>&#8221; means, with respect to a Party or its Affiliate or Sublicensee, GAAP or IFRS, as such Person uses for its financial reporting standards from time to
                      time, in each case, as consistently applied.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z260e510c5a454281813a2ae4db346641" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.2</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Affiliate</font>&#8221; means, with respect to a Person, any corporation or other business entity controlled by, controlling, or under common control with such Person, with &#8220;control&#8221;
                      meaning (a) direct or indirect beneficial ownership of more than 50% of the voting stock or other ownership interest of, or more than 50% interest in the income of, the applicable entity, or (b) the possession, directly or indirectly,
                      of the power to direct the management or policies of the applicable entity, whether through the ownership of voting securities or other equity rights, by contract relating to voting rights or corporate governance, or otherwise.
                      Notwithstanding the foregoing, for purposes of this Agreement, &#8220;Affiliates&#8221; will not include, (a) with respect to an entity, <font style="font-style: italic;">bona fide</font> venture capital investors in such entity or <font style="font-style: italic;">bona fide</font> institutional investors in such entity, in each case, that routinely make venture capital investments for the potential financial return on such investments and not with any view to
                      acquisition or for other strategic purpose, or Affiliates of such venture capital or institutional investors, or (b) with respect to Otsuka, any entities that are controlled by Otsuka Holdings Co., Ltd. but are not subsidiaries of
                      Otsuka.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z5d601ea9fe9f45879abc744c06cdea4a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.3</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Alliance Manager</font>&#8221; has the meaning set forth in <u>Section 8.8</u> (Alliance Managers).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z25ac2c4636d041f0b3c1d7f97d8685d4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.4</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***<font style="font-weight: bold; font-style: italic;">]</font>&#8221; means any [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf7f807d2fc20402d8a57256f374b0e1f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.5</td>
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                    <div><font style="font-weight: bold; font-style: italic;">&#8220;American Commercialization Operating Plan&#8221;</font> has the meaning set forth in <u>Section 6.4.1</u> (Global Brand Strategy and American Commercialization Operating Plan).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.6</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">American Medical Affairs Operating Plan</font>&#8221; has the meaning set forth in <u>Section 6.6.1</u> (Global Medical Affairs Strategy and American Medical Affairs Operating Plan).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.7</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ancillary Agreements</font>&#8221; means the Pharmacovigilance Agreement, each Supply Agreement, and each Quality Agreement.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.8</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Applicable Law</font>&#8221; means applicable (with respect to the particular activity, task, or obligation under this Agreement to which such term applies) laws, statutes, rules,
                      regulations, and other pronouncements having the effect of law of any Governmental Authority that may be in effect from time to time, including for clarity any applicable rules, regulations, guidelines, or other requirements of any
                      Regulatory Authority that may be in effect from time to time.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.9</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Approved Labeling</font>&#8221; means, with respect to a Licensed Product and a jurisdiction: (a) the applicable Regulatory Authority-approved full prescribing information for such
                      Licensed Product in such jurisdiction; and (b) the applicable Regulatory Authority-approved labels and any other written, printed, or graphic materials on any container, wrapper, or any package insert that is used with or for such
                      Licensed Product in such jurisdiction.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.10</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Asia JSC</font>&#8221; has the meaning set forth in <u>Section 8.2.1</u> (Formation and Purposes of the Joint Steering Committees).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.11</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Asia ROFN Period</font>&#8221; has the meaning set forth in <u>Section 2.8.1</u> (ROFN Exercise).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="za0e49e37ab5548dcbbc63f0d4606670a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.12</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Asia-Specific Non-Clinical HAE Development Activities</font>&#8221; has the meaning set forth in <u>Section 4.2.2(b)</u> (Asia Territory).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze24198daef8548eb8841731a38dc326b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.13</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Asia Territory</font>&#8221; means, individually, each of the Major Asian Countries, Australia, Egypt, Hong Kong, Indonesia, Malaysia, Myanmar, New Zealand, Pakistan, the Philippines,
                      Singapore, Taiwan, Thailand, Turkey, and Vietnam, excluding all countries in any Terminated Region.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z9f913558c41b414f8cc83412d1de367e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.14</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Asia Territory Brand Strategy&#8221; </font>has the meaning set forth in <u>Section 6.4.2</u> (Otsuka Territory Brand Strategy and Commercialization Operating Plans).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze2af19dd562c4cd092c3ac3515585346" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.15</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Asia Territory Commercialization Operating Plan</font>&#8221; has the meaning set forth in <u>Section 6.4.2</u> (Otsuka Territory Brand Strategy and Commercialization Operating
                      Plans).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zdfc4ef48a86e4a9ca6bc785d3103ae13" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.16</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Asia Territory Medical Affairs Plan</font>&#8221; has the meaning set forth in <u>Section 6.6.2</u> (Otsuka Territory Medical Affairs Plans).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf0fd39e3c1f845c991e717e5f0099654" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.17</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Asia Territory-Specific Development Plan</font>&#8221; has the meaning set forth in <u>Section 4.3.2</u> (Asia Territory-Specific Development Plan).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z84373f78d579470b974e8f02839bb9b0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.18</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">ASMF</font>&#8221; has the meaning set forth in <u>Section 5.3</u> (Correspondences with Regulatory Authorities).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z3d7bb0e1d0c6493682f2ea16a4c9143e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.19</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Blocking Identified Rights</font>&#8221; has the meaning set forth in <u>Section 2.7.2(a)(ii)</u> (Acquisition of Potential In-Licenses).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zdf110e2da156493eb38e08bc095d87f4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.20</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Breach Notification</font>&#8221; has the meaning set forth in <u>Section 14.2.1</u> (Material Breach).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z1c3b7222433c4d318568f461db4509a9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.21</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Business Day</font>&#8221; means a day other than (a) a Saturday, Sunday, (b) a day on which banking institutions in California, Tokyo, Japan, or London, England are required by
                      Applicable Law to remain closed or (c) the nine consecutive days beginning on December 24 and continuing through January 1, to the extent not already covered in clause (a) or clause (b).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z9b44e9ec10394619810c12e9e2573fde" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.22</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Calendar Quarter</font>&#8221; means, with respect to the first Calendar Quarter during the Term, the period beginning on the Restatement Date and ending on the last day of the
                      Calendar Quarter within which the Restatement Date falls, and thereafter each successive period of three calendar months ending on (and including) each of March 31, June 30, September 30, and December 31; except that the last Calendar
                      Quarter during the Term will end upon the expiration of the Term.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zaa3899ee52a3435788d468a277cf2c51" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.23</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Calendar Year</font>&#8221; means the period of 12 consecutive calendar months beginning on January 1 and ending on December 31; except that (a) the first Calendar Year during the
                      Term will begin on the Restatement Date and end on December 31 of the Calendar Year within which the Restatement Date falls, and (b) the last Calendar Year during the Term will end upon expiration of the Term.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.24</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Change of Control</font>&#8221; means, with respect to a Party, that: (a) any Third Party acquires directly or indirectly the beneficial ownership of any voting security of such
                      Party, or if the percentage ownership of such Third Party in the voting securities of such Party is increased through stock redemption, cancellation, or other recapitalization, and immediately after such acquisition or increase such
                      Third Party is, directly or indirectly, the beneficial owner of voting securities representing more than 50% of the total voting power of all of the then outstanding voting securities of such Party; (b) a merger, consolidation,
                      recapitalization, or reorganization of such Party is consummated that would result in shareholders or equity holders of such Party immediately prior to such transaction owning 50% or less of the outstanding voting securities of the
                      surviving entity (or its parent entity) immediately following such transaction; or (c) the sale or transfer to a Third Party, in one or more related transactions, of all or substantially all of such Party&#8217;s consolidated assets taken
                      as a whole.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zfa6e0ffb02b245d6965a957c20ade12f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.25</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Clinical Supply Agreement</font>&#8221; has the meaning set forth in <u>Section 7.2.1</u> (Clinical Supply Agreement).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z7cb7a6847c4e4a379b7441b1dab6493f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.26</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Clinical Trial</font>&#8221; means any clinical trial in humans.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zc6dda526a7ff44c0a701136bd1755be7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.27</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">CMC</font>&#8221; means chemistry, manufacturing, and controls.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.28</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">CMO</font>&#8221; has the meaning set forth in <u>Section 7.3.1</u> (By Otsuka).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zeed7dd7189f74e52b45ff7b416ac7a40" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.29</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Collaboration In-License</font>&#8221; means (a) any Potential In-License that [***] in accordance with <u>Section 2.7.2(b)</u> (Collaboration In-Licenses) and (b) any Existing
                      Third-Party IP Agreement.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zc03fafe794a540d29d53c3f04e5b8fce" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.30</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Collaboration Know-How</font>&#8221; means all Know-How developed or invented by a Party&#8217;s or its Affiliates&#8217;, licensees&#8217;, Sublicensees&#8217;, or Subcontractors&#8217; employees, agents, or
                      independent contractors, or any Persons contractually required to assign or license such Know-How to such Party or any Affiliate of such Party, either alone or jointly with the other Party&#8217;s or its Affiliates&#8217;, licensees&#8217;,
                      Sublicensees&#8217;, or Subcontractors&#8217; employees, agents, or independent contractors, or any Persons contractually required to assign or license such Know-How to such other Party or any Affiliate of such other Party, in each case, in the
                      performance of activities under the Original Agreement during the Original Agreement Term or under this Agreement during the Term.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zb2428849472047f0980c2a7476ca89f8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.31</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Collaboration Patent Rights</font>&#8221; means any Patent Right that (a) has a priority date after the Original Effective Date and (b) Covers any Invention included in the
                      Collaboration Know-How.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="za4169451fe2148cf90d0e06aa562e606" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.32</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Combination Product</font>&#8221; has the meaning set forth in <u>Section 1.158</u> of this <u>Appendix 1</u> (Definitions).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z55e14133cb034ff1beae1b79c925e595" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.33</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Combination Product Net Sales</font>&#8221; has the meaning set forth in <u>Section 1.158</u> of this <u>Appendix 1</u> (Definitions).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zd4878209a8944d6f944c6877bf148565" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.34</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Commercial Supply Agreement</font>&#8221; has the meaning set forth in <u>Section 7.2.2</u> (Commercial Supply Agreement).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zbea921c321d84de5a31b94e16b06c4bd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.35</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Commercialization</font>&#8221; means any and all activities directed to the marketing, promotion, distribution, pricing, reimbursement, offering for sale, and sale of a
                      pharmaceutical or biologic product and interacting with Regulatory Authorities following receipt of Regulatory Approval in the applicable country or region for such pharmaceutical or biologic product regarding the foregoing, including
                      seeking and maintaining any required Reimbursement Approval, but excluding activities directed to Manufacturing or Development. &#8220;<font style="font-weight: bold; font-style: italic;">Commercialize</font>,&#8221; &#8220;<font style="font-weight: bold; font-style: italic;">Commercializing</font>,&#8221; and &#8220;<font style="font-weight: bold; font-style: italic;">Commercialized</font>&#8221; will be construed accordingly.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.36</td>
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                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Commercially Reasonable Efforts</font>&#8221; means, with respect to the Exploitation of a Licensed Product by a Party, [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.37</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Competitive Infringement</font>&#8221; means any infringement, unauthorized use, misappropriation or threatened infringement or misappropriation by a Third Party with respect to any
                      Ionis Technology, Otsuka Technology, or Joint Collaboration Technology by reason of the making, using, offering to sell, selling, or importing of a compound, product, method, or process that would be competitive with a Licensed
                      Product then being Developed or Commercialized in the Field.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.38</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Confidential Disclosure Agreement</font>&#8221; has the meaning set forth in <u>Section 16.2</u> (Entire Agreement; Amendment).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.39</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Confidential Information</font>&#8221; means, subject to <u>Section 12.3</u> (Exemptions), (a) Know-How and any technical, scientific, trade, research, Manufacturing, business,
                      financial, marketing, product, supplier, intellectual property, and other non-public or proprietary data or information (including unpublished patent applications) that may be disclosed by one Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Disclosing Party</font>&#8221;) or its Affiliates to the other Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Receiving Party</font>&#8221;) or its Affiliates pursuant to this Agreement (including
                      information disclosed prior to the Restatement Date pursuant to the Confidential Disclosure Agreement or the Original Agreement), regardless of whether such information is specifically marked or designated as confidential and
                      regardless of whether such information is in written, oral, electronic, or other form, and (b) the terms of this Agreement.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.40</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Continuing Know-How Transfer</font>&#8221; has the meaning set forth in <u>Section 3.1</u> (Initial Know-How Transfer).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.41</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div><font style="font-weight: bold;">&#8220;</font><font style="font-weight: bold; font-style: italic;">Control</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Controlled</font>&#8221; means the possession by a Party (whether by
                      ownership, license, or otherwise other than pursuant to this Agreement) of, (a) with respect to any materials or other tangible Know-How, the legal authority or right to physical possession of such materials or tangible Know-How, with
                      the right to provide such materials or tangible Know-How to the other Party on the terms set forth herein, (b) with respect to Patent Rights, Regulatory Approvals, Regulatory Submissions, intangible Know-How, or other intellectual
                      property, the legal authority or right to grant a license, sublicense, access, or right to use (as applicable) to the other Party under such Patent Rights, Regulatory Approvals, Regulatory Submissions, intangible Know-How, or other
                      intellectual property on the terms set forth herein, in each case ((a) and (b)), without breaching or otherwise violating the terms of any arrangement or agreement with a Third Party in existence as of the time such Party or its
                      Affiliates would first be required hereunder to grant the other Party such access, right to use, licenses, or sublicense or incurring any additional payment obligations to a Third Party that would not be incurred but for such access,
                      right to use, licenses, or sublicense, other than payment obligations incurred under a Collaboration In-License, and (c) with respect to any product, the possession by a Party of the ability (whether by sole or joint ownership,
                      license, or otherwise, other than pursuant to the licenses granted under this Agreement) to grant an exclusive license or sublicense of Patent Rights that Cover such product or proprietary Know-How that is used in connection with the
                      Exploitation of such product. Notwithstanding the foregoing, [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.42</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Core or Manufacturing Identified Rights</font>&#8221; has the meaning set forth in <u>Section 2.7.2(a)(i)</u> (Acquisition of Potential In-Licenses).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z95ae0a4a8b83431f90f19b4c7911ec13" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.43</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Core or Manufacturing Potential In-License</font>&#8221; has the meaning set forth in <u>Section 2.7.2(a)(i) </u>(Acquisition of Potential In-Licenses).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.44</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Cost Overrun</font>&#8221; has the meaning set forth in <u>Section 4.4.2(b)</u> (Cost Overruns).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.45</td>
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                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Cover</font>&#8221; means, with respect to a particular subject matter at issue and a relevant Patent Right or individual claim in such Patent Right, as applicable, that the
                      manufacture, use, sale, offer for sale, or importation of such subject matter would fall within the scope of one or more claims in such Patent Right.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.46</td>
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                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Cross-Territory Clinical Development Plan</font>&#8221; has the meaning set forth in <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.47</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Cross-Territory Clinical Studies</font>&#8221; has the meaning set forth in <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z50cae2632cd34eb29e2f726823582ca6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.48</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Debarred/Excluded</font>&#8221; has the meaning set forth in <u>Section 11.1.5</u> (Mutual Representations and Warranties).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.49</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Development</font>&#8221; means all internal and external research, development and regulatory activities regarding pharmaceutical or biologic products, including (a) research,
                      process development, non-clinical testing, toxicology, non-clinical activities, IND-enabling studies, and Clinical Trials, and (b) preparation, submission, review, and development of data or information for the purpose of submission
                      to a Regulatory Authority to obtain authorization to conduct Clinical Trials and to obtain, support, or maintain Regulatory Approval of a pharmaceutical or biologic product, but excluding activities directed to Manufacturing or
                      Commercialization. Development will include development and regulatory activities for additional presentations or indications for a product after receipt of Regulatory Approval of such product, including Post-Approval Mandatory
                      Studies. &#8220;<font style="font-weight: bold; font-style: italic;">Develop</font>,&#8221; &#8220;<font style="font-weight: bold; font-style: italic;">Developing</font>,&#8221; and &#8220;<font style="font-weight: bold; font-style: italic;">Developed</font>&#8221; will
                      be construed accordingly.</div>
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                </tr>

            </table>
            <div>&#160;</div>
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                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.50</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Disclosing Party</font>&#8221; has the meaning set forth in <u>Section 1.39</u> (Confidential Information) of this <u>Appendix 1</u> (Definitions).</div>
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                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.51</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Disputed Matter</font>&#8221; has the meaning set forth in <u>Section 15.1</u> (Executive Officers; Disputes).</div>
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                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.52</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Eligible Cross-Territory Development Costs</font>&#8221; has the meaning set forth in <u>Section 4.4.3</u> (Shared Cross-Territory Development Costs).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze7d766a74f174b719cf1a72a5975a136" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.53</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">EMA</font>&#8221; means the European Medicines Agency or any successor agency thereto.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z06b59b94da2c47399e92c9258648b2c5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.54</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Establishing Committee</font>&#8221; has the meaning set forth in <u>Section 8.3.1</u> (Formation; Authority).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zc547090455914ad99a1bc90f651108a3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.55</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Europe JSC</font>&#8221; has the meaning set forth in <u>Section 8.2.1</u> (Formation and Purposes of the Joint Steering Committees).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z743bdb78b2914b55b2b283a3dcbe6cb8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.56</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Europe Regulatory Subcommittee</font>&#8221; has the meaning set forth in <u>Section 5.2</u> (Europe Regulatory Subcommittee).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z0990f379e3f84c73820148b8eff0c040" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.57</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Europe ROFN Period</font>&#8221; has the meaning set forth in <u>Section 2.8.1</u> (ROFN Exercise).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z64f4e3d0d1a845e2b977b9fae51e0a9b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.58</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Europe Territory</font>&#8221; means (a) all members of the European Union or the European Economic Area (EEA) as of the Original Effective Date, and (b) the following countries:
                      Iceland, Liechtenstein, Norway, Switzerland, and the United Kingdom, excluding all countries in any Terminated Region.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z9349e8450b224a7eb5e1179631e276c7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.59</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Europe Territory Brand Strategy</font>&#8221; has the meaning set forth in <u>Section 6.4.2</u> (Otsuka Territory Brand Strategy and Commercialization Operating Plans).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="zd2f543fe157a4492875df6974eb9d4c5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.60</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Europe Territory Commercialization Operating Plan</font>&#8221; has the meaning set forth in <u>Section 6.4.2</u> (Otsuka Territory Brand Strategy and Commercialization Operating
                      Plans).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z1cbfcae3f4f64b26a1899cdf636aec5e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.61</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Europe Territory Medical Affairs Plan</font>&#8221; has the meaning set forth in <u>Section 6.6.2</u> (Otsuka Territory Medical Affairs Plans).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zff5c971bed984971bc236cd35433960b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.62</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Europe Territory-Specific Development Plan</font>&#8221; has the meaning set forth in <u>Section 4.3.1</u> (Europe Territory-Specific Development Plan).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z126eafe217e44907862c81a5d0b6158b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.63</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">European Union</font>&#8221; or &#8220;<font style="font-weight: bold;">E.U.</font>&#8221; means the economic, scientific, and political organization of member states of the European Union as it
                      may be constituted from time to time.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze1bdef0950eb4a6396f61547cc99c6bf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.64</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ex-Japan Asia Territory</font>&#8221; means the Asia Territory, except for Japan.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.65</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 7.2.6</u> ([***]).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zb5a5f5b182aa466d84db650c6b57bb5a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.66</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Executive Committee</font>&#8221; has the meaning set forth in <u>Section 8.1.1</u> (Formation and Purpose of the Executive Committee).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf6dccf1b64634f09bac0c86b3bab965d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.67</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Executive Committee Co-Chairperson</font>&#8221; has the meaning set forth in <u>Section 8.1.2</u> (Membership).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze65c4615ad874f25a52ac501a8de6c24" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.68</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Executive Officer</font>&#8221; means (a) with respect to Otsuka, its President and Representative Director or their designee and (b) with respect to Ionis, the Chief Executive
                      Officer or their designee.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z6d336fb697d04e1a997b8a8faef98c4b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.69</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Existing Third-Party IP Agreement</font>&#8221; means any agreement between Ionis (or any of its Affiliates) and any Third Party entered into prior to the Original Effective Date or
                      any time during the Original Agreement Term under which Ionis (or any of its Affiliates) obtained a license or other right to any of such Third Party&#8217;s Know-How or Patent Rights that fall within the definition of any of the Ionis
                      Technology.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z9cef976cc66f4b1babf9958eeeb0410b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.70</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Exploit</font>&#8221; means to make, have made, use, offer to sell, sell, Develop, Manufacture, Commercialize, or otherwise exploit. &#8220;<font style="font-weight: bold; font-style: italic;">Exploitation</font>&#8221; will be construed accordingly.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zb57ba16dd06e4b0d9257eec0ad6330c9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.71</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">External Costs</font>&#8221; mean, with respect to a Party, the documented actual expenses paid to Third Parties (or payable to Third Parties and accrued in accordance with such
                      Party&#8217;s Accounting Standards) by such Party (or its Affiliate) in consideration of the performance of activities under this Agreement, without mark-up, and excluding any costs or expenses included under the FTE Rate.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zdd2f49a643614b78ad04e2e3530b3745" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.72</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">FD&amp;C Act</font>&#8221; means the United States Federal Food, Drug and Cosmetic Act, as amended from time-to-time, together with any rules, regulations, and requirements
                      promulgated thereunder (including all additions, supplements, extensions, and modifications thereto).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="za5f0b475373e43349515d5cedb6f06d1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.73</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">FDA</font>&#8221; means the U.S. Food and Drug Administration or any successor agency thereto.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z846a918d39374ebdb5863ea802ef5392" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.74</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Field</font>&#8221; means for the treatment or prevention of any diseases and conditions in humans.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="za55410b099aa4e1cbc23c8440bd210f2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.75</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Filing Party</font>&#8221; has the meaning set forth in <u>Section 5.5</u> (Regulatory Submissions).</div>
                  </td>
                </tr>

            </table>
            <div><br>
            </div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="z0d8fad58585b4566a439e21ccc9e1cfa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.76</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">First Commercial Sale</font>&#8221; means, with respect to a Licensed Product in a country, the first sale for end use or consumption to a Third Party of such Licensed Product in such
                      country by a Party, or its Affiliates or Sublicensees after the receipt of Regulatory Approval and Reimbursement Approval in the Field for such Licensed Product by the relevant Regulatory Authority in such country. First Commercial
                      Sale excludes any sale or other distribution for use in a Clinical Trial or other Development activity or for compassionate use,<font style="font-size: 12pt;">&#160;</font>named-patient use, or expanded access, indigent or other patient
                      access programs when sold or distributed at or below the applicable Selling Party&#8217;s costs.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z217c3dee6057436b91d8eebc09599757" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.77</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***<u>]</u>&#8221; has the meaning set forth in <u>Section 9.3.4(a)</u> ([***]).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z8ffbd166a3a04ed48fdcb193460a89cc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.78</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Product</font>&#8221; has the meaning set forth in <u>Section 2.8.1</u> (ROFN Exercise).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z791552d8befa4d9faff977118623d7bd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.79</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Product Activities</font>&#8221; has the meaning set forth in <u>Section 2.8.3</u> (Follow-On Product Activities).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z368cfdb3f27b4af987c29f39373802f7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.80</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Force Majeure</font>&#8221; has the meaning set forth in <u>Section 16.5</u> (Force Majeure).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z99382202c09a41babf47f54c79f92a98" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.81</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">FTE</font>&#8221; means the equivalent of the work of one duly qualified employee of a Party full time for one year (consisting of a total of [***] hours per year) directly carrying
                      out [***] activities under this Agreement. Overtime, and work on weekends, holidays and the like will not be counted with any multiplier (<font style="font-style: italic;">e.g.</font>, time-and-a-half or double time) toward the number
                      of hours that are used to calculate the FTE contribution, and no individual may be charged at greater than one FTE, regardless of that individual&#8217;s hours worked during that year. The portion of an FTE billable by a Party for one
                      employee during a given accounting period will be determined by dividing the number of hours worked directly by such employee on the work to be conducted under this Agreement during such accounting period by the number of FTE hours
                      applicable for such accounting period based on [***] working hours per Calendar Year. For clarity, travel time spent by an employee, unless also spent working directly on activities under this Agreement, will not be included in the
                      number of hours used to calculate the FTE contribution.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z8def03939102440990607e752e4e876b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.82</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">FTE Rate</font>&#8221; means ***] per FTE per hour. For the avoidance of doubt, such FTE Rate will be [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z2df96aad32e349f0aa3a5e8421426552" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.83</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Future Cross-Territory Studies</font>&#8221; has the meaning set forth in <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z6eadcac6fd294438a0e0763a45c29d7b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.84</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">GAAP</font>&#8221; means the generally accepted accounting principles in the United States.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zc8776508caeb445abd24c6e7d9960ce5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.85</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Generic Product</font>&#8221; means, with respect to a Licensed Product in a country, a pharmaceutical product (other than such Licensed Product) that (a) is expected to be sold by a
                      Third Party other than a Sublicensee under license from Otsuka in such country, (b) is authorized for use in such country in one or more of the indications for which such Licensed Product has Regulatory Approval in such country; and
                      (c) contains the same active pharmaceutical ingredient(s) as such Licensed Product. A product will not be considered to be a Generic Product if (i) Otsuka or any of its Affiliates or Sublicensees was involved in or authorized the
                      Development or Commercialization of such product, (ii) Otsuka or any of its Affiliates or Sublicensees has granted a license to such Third Party in respect of such product, or (iii) such product is Commercialized by any Person who
                      obtained such product in a chain of distribution that included Otsuka or any of its Affiliates or Sublicensees.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zd378cfb744b3475695106a2423e039cd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.86</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Global Brand Strategy</font>&#8221; has the meaning set forth in <u>Section 6.4.1</u> (Global Brand Strategy and American Commercialization Operating Plan).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="z4d16553500b54833aeec0cbe3d3588fc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.87</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Global Medical Affairs Strategy</font>&#8221; has the meaning set forth in <u>Section 6.6.1</u> (Global Medical Affairs Strategy and American Medical Affairs Operating Plan).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z14c2f29592a243a8b6eefae247dc962e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.88</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Global Trade Control Laws</font>&#8221; means the U.S. Export Administration Regulations, the U.S. International Traffic in Arms Regulations, the economic sanctions regulations
                      administered by the U.S. Treasury Department&#8217;s Office of Foreign Assets Control, E.U. Council Regulations on export controls, including Nos. 428/2009, 267/2012, other E.U. Council sanctions regulations, as implemented in the E.U.
                      member states, United Nations sanctions policies, and all relevant regulations made under any of the foregoing.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z603ef78ba20744158c549b0be52724af" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.89</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Good Clinical Practices</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">GCP</font>&#8221; means the then-current good clinical practice standards, practices, and
                      procedures promulgated or endorsed by the applicable Regulatory Authority as set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time-to-time.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z760f1b4e07bc433491c05bd57c22b4e7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.90</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Good Laboratory Practices</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">GLP</font>&#8221; means the then-current good laboratory practice standards, practices, and
                      procedures promulgated or endorsed by the applicable Regulatory Authority as set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time-to-time.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze13a565afaae4bc6b867a116b3d9ae90" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.91</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Good Manufacturing Practices</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">GMP</font>&#8221; means the then-current good manufacturing practice standards,
                      practices, and procedures promulgated or endorsed by the applicable Regulatory Authority as set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time-to-time.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z74f329652da64a7b92c607427d2e1885" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.92</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Government Official</font>&#8221; means any official, officer, employee, or representative of: (a) any federal, state, provincial, administrative division, county, or municipal
                      government or any department or agency thereof; (b) any public international organization or any department or agency thereof; or (c) any company or other entity owned or controlled by any government or Governmental Authority.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zfdb1bf27df1e43fc92ff22b0a8e84378" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.93</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Governmental Authority</font>&#8221; means any court, agency, department, authority, tribunal, or other instrumentality of any supra-national, national, state, provincial, county,
                      city, or other political subdivision. For clarity, Governmental Authorities include all Regulatory Authorities.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z76d51c23d55e476482aa002dc38bd208" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.94</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">HAE</font>&#8221; means hereditary angioedema.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z6e349b6ea6164cfb9bcec43284cc5a06" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.95</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Identified Rights</font>&#8221; has the meaning set forth in <u>Section 2.7.1</u> (Identification of New In-License Agreements).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="za9f4bd571dc54d66a975854bdfa72362" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.96</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">IFRS</font>&#8221; means International Financial Reporting Standards, consistently applied.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z50c4b4fd34af4185bf6fd963ed7d21a9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.97</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">IND</font>&#8221; means an Investigational New Drug application required pursuant to 21 C.F.R. Part 312 or any comparable filings outside of the U.S. required to commence human
                      clinical trials in such country or region (such as an application for a Clinical Trial Authorization in the E.U.), and all supplements or amendments that may be filed with respect to the foregoing.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zd15cda252c3645ddb1b31911b65bb7fd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.98</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Indemnified Party</font>&#8221; has the meaning set forth in <u>Section 13.3</u> (Indemnification Procedure).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z4594da66db8043ac93a2322293e5d61c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.99</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Indemnifying Party</font>&#8221; has the meaning set forth in <u>Section 13.3</u> (Indemnification Procedure).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="zb5d4163733694ddb9e47706c64811b5e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.100</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Initial Know-How Transfer</font>&#8221; has the meaning set forth in <u>Section 3.1</u> (Initial Know-How Transfer).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z79730142da5b43eca09827c546d559f3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.101</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Initial Royalties</font>&#8221; has the meaning set forth in <u>Section 9.3.1</u> (Royalty Payments During the Initial Royalty Term).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf42f243bff704c179079f0c0bea7e5ac" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.102</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Initial Royalty Term</font>&#8221; has the meaning set forth in <u>Section 9.3.1</u> (Royalty Payments During the Initial Royalty Term).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf4162d1c22ff43cba8865c3e6ecadbea" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.103</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Initiation</font>&#8221; means dosing of the first patient in a Clinical Trial.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z6f7faf44ca2640668b0a472d238785e0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.104</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Internal Costs</font>&#8221; means, for any period of time, the product obtained by multiplying (a) the total FTEs (or portion thereof) devoted to the performance of activity under
                      this Agreement during such period, by (b) the applicable FTE Rate for such period; <font style="font-style: italic;">provided </font>that [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z984a019d047f4af883f07674c37ef9da" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.105</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Invention</font>&#8221; means any process, method, composition of matter, article of manufacture, discovery, or finding that is conceived or reduced to practice (whether or not
                      patentable).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z77199172f4164366b893c2db89ffc79c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.106</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Attribution Language</font>&#8221; has the meaning set forth in <u>Section 12.7.2</u> (Acknowledgement).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z883d25f135d14bad9e6a99545c6df132" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.107</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Know-How</font>&#8221; has the meaning set forth in <u>Section 10.1.2(a)</u> (Ownership of Arising Intellectual Property).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z2c0738f86c5241f8981ee403af45961b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.108</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Patent Rights</font>&#8221; has the meaning set forth in <u>Section 10.1.2(a)</u> (Ownership of Arising Intellectual Property).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zdc6a3221bc234d0e9e20990fcaee33fa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.109</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Core Technology</font>&#8221; means Ionis Core Technology Know-How and the Ionis Core Technology Patents.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zed44d5241a844f908a793ea7dc8c0f31" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.110</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Core Technology Know-How</font>&#8221; means, subject to <u>Section 4.4.4(b)</u> ([***] by Ionis), all Know-How, including Ionis Collaboration Know-How but excluding Ionis
                      Product-Specific Know-How, Ionis Manufacturing and Analytical Know-How and Ionis&#8217; interest in any Joint Collaboration Know-How, that (a) is Controlled by Ionis or its Affiliates as of the Original Effective Date or at any time during
                      the Original Agreement Term or the Term, (b) is necessary or reasonably useful to Exploit a Licensed Product, and (c) relates generally to oligonucleotide.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zcaf0d45a05434844914bca8bf51344aa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.111</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Core Technology Patents</font>&#8221; means, subject to <u>Section 4.4.4(b)</u> ([***] by Ionis), any Patent Rights, including Ionis Collaboration Patent Rights but excluding
                      Ionis Product-Specific Patents, Ionis Manufacturing and Analytical Patents and Ionis&#8217; interest in any Joint Collaboration Patent Rights, that (a) are Controlled by Ionis or its Affiliates as of the Original Effective Date or at any
                      time during the Original Agreement Term or the Term, (b) are necessary or reasonably useful (or, with respect to patent applications, would be necessary or reasonably useful if such patent applications were to issue as patents) to
                      Exploit a Licensed Product and (c) Cover subject matter generally applicable to oligonucleotides. <font style="color: rgb(0, 0, 0);">A list of the </font>Ionis Core Technology Patents <font style="color: rgb(0, 0, 0);">as of the
                        Restatement </font>Date <font style="color: rgb(0, 0, 0);">is set forth on </font><font style="font-variant: small-caps; color: rgb(0, 0, 0);"><u>Schedule 1.111</u></font><font style="color: rgb(0, 0, 0);"> (Ionis Core Technology
                        Patents)</font>; <font style="font-style: italic;">provided</font> that, any Patent Right existing as of the Restatement Date that otherwise would be included in the definition of Ionis Core Technology Patents but is not included
                      on <font style="font-variant: small-caps; color: rgb(0, 0, 0);"><u>Schedule 1.111</u></font><font style="color: rgb(0, 0, 0);"> (Ionis Core Technology Patents) </font>will still be considered an Ionis Core Technology Patent<font style="color: rgb(0, 0, 0);">.</font></div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z67349e41a22b4906b5f63d6ab3ea5781" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.112</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Incurred Development Costs</font>&#8221; has the meaning set forth in <u>Section 4.4.1(c)(ii)</u> (Shared Development Costs).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="zeddd3b839ef049fb8fb34be3cae8adb2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.113</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Indemnitee</font>&#8221; has the meaning set forth in <u>Section 13.2</u> (Indemnification by Otsuka).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z89381bc089604a11aa626a5f85b1a72a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.114</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Internal Oligonucleotide Safety Database</font>&#8221; has the meaning set forth in <u>Section 5.12.1</u> (Ionis Internal Oligonucleotide Safety Database).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z677a10b2f3074a39bec90d987b0cc245" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.115</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Know-How</font>&#8221; means the Ionis Core Technology Know-How, Ionis Manufacturing and Analytical Know-How, and Ionis Product-Specific Know-How.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z3c7b8038bfce484ebe5706c1d6a5826c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.116</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Manufacturing and Analytical Know-How</font>&#8221; means, subject to <u>Section 4.4.4(b)</u> ([***] by Ionis), Know-How, including Ionis Collaboration Know-How but excluding
                      Ionis&#8217; interest in any Joint Collaboration Know-How, that (a) is Controlled by Ionis or its Affiliates as of the Original Effective Date or at any time during the Original Agreement Term or the Term, (b) is necessary or reasonably
                      useful to Exploit a Licensed Product, and (c) relates to any Manufacturing Technology.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z958df43d237046dba55fe747395466df" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.117</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Manufacturing and Analytical Patents</font>&#8221; means, subject to <u>Section 4.4.4(b)</u> ([***] by Ionis), Patent Rights, including Ionis Collaboration Patent Rights but
                      excluding Ionis&#8217; interest in any Joint Collaboration Patent Rights, that (a) are Controlled by Ionis or its Affiliates as of the Original Effective Date or at any time during the Original Agreement Term or the Term, (b) are necessary
                      or reasonably useful (or, with respect to patent applications, would be necessary or reasonably useful if such patent applications were to issue as patents) to Exploit a Licensed Product, and (c) Cover Manufacturing Technology. A list
                      of Ionis Manufacturing and Analytical Patents as of the Restatement Date is set forth on <font style="font-variant: small-caps;"><u>Schedule 1.117</u></font> (Ionis Manufacturing and Analytical Patents); <font style="font-style: italic;">provided</font> that, any Patent Right existing as of the Restatement Date that otherwise would be included in the definition of Ionis Manufacturing and Analytical Patent but is not included on <font style="font-variant: small-caps;"><u>Schedule 1.117</u></font> (Ionis Manufacturing and Analytical Patents) will still be considered an Ionis Manufacturing and Analytical Patent.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zae412d859461482cb633bcb199688c2a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.118</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Manufacturing and Analytical Technology</font>&#8221; means Ionis Manufacturing and Analytical Know-How and Ionis Manufacturing and Analytical Patents.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z6c1b4f327047450787d91f6fa71d090b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.119</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis [</font>***<font style="font-weight: bold; font-style: italic;">] Costs</font>&#8221; has the meaning set forth in <u>Section 4.4.4(c)</u> (Otsuka Opt-In).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf3195c01745043918a7ffee993514fcc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.120</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis [</font>***<font style="font-weight: bold; font-style: italic;">] Development</font>&#8221; has the meaning set forth in <u>Section 4.4.4(b)</u> ([***] by Ionis).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z31a607eb1e0440f184894a21d914b6b2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.121</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis [</font>***<font style="font-weight: bold; font-style: italic;">]</font>&#8221; means [***] generated by or on behalf of Ionis in the [***] in accordance with <u>Section
                        4.4.4(b)</u> ([***] by Ionis).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zdad498e229854106939c88a7a6eda1a8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.122</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Patent Rights</font>&#8221; means the Ionis Core Technology Patents, Ionis Manufacturing and Analytical Patents, and Ionis Product-Specific Patents.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z41259d0822294401a1792953cc8cf49f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.123</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product-Specific Know-How</font>&#8221; means, subject to <u>Section 4.4.4(b)</u> ([***] by Ionis), all Know-How, including Ionis Collaboration Know-How but excluding Ionis&#8217;
                      interest in any Joint Collaboration Know-How, that is (a) Controlled by Ionis or its Affiliates as of the Original Effective Date or at any time during the Original Agreement Term or the Term, (b) necessary or reasonably useful to
                      Exploit a Licensed Product in the Field, and (c) specifically relating to (i) the composition of matter of a Licensed Product or (ii) methods of using a Licensed Product for the Field; <font style="font-style: italic;">provided
                        however</font>, Know-How that (i) consists of subject matter applicable to oligonucleotide compounds or products in general or (ii) relates to an oligonucleotide compound that does not specifically modulate expression of PKK via the
                      binding, partially or wholly, of such compound to RNA that encodes PKK, will not be considered Ionis Product-Specific Know-How, and in each case of (i) and (ii), such Know-How will be considered Ionis Core Technology Know-How.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.124</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product-Specific Patents</font>&#8221; means, subject to <u>Section 4.4.4(b)</u> ([***] by Ionis), all Product-Specific Patents, excluding Ionis&#8217; interest in any Joint
                      Collaboration Patent Rights, that are (a) Controlled by Ionis or its Affiliates as of the Original Effective Date or at any time during the Original Agreement Term or the Term and (b) necessary or reasonably useful (or, with respect
                      to patent applications, would be necessary or reasonably useful if such patent applications were to issue as patents) to Exploit a Licensed Product; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that Patent Rights that include only claims that are directed to (i) subject matter applicable to oligonucleotide compounds or products in general or (ii) an oligonucleotide compound that does not
                      specifically modulate expression of PKK via the binding, partially or wholly, of such compound to RNA that encodes PKK, will not be considered Ionis Product-Specific Patents, and in each case of (i) and (ii), such Patent Rights will
                      be considered Ionis Core Technology Patents<font style="color: rgb(0, 0, 0);">. A list of </font>Ionis Product-Specific Patents <font style="color: rgb(0, 0, 0);">as of the </font>Restatement Date <font style="color: rgb(0, 0, 0);">is set forth on </font><font style="font-variant: small-caps;"><u>Schedule 1.124</u></font> (Ionis Product-Specific Patents); <font style="font-style: italic;">provided</font> that, any Patent Right existing as of the
                      Restatement Date that otherwise would be included in the definition of Ionis Product-Specific Patent but is not included on <font style="font-variant: small-caps;"><u>Schedule 1.124</u></font> (Ionis Product-Specific Patents) will
                      still be considered an Ionis Product-Specific Patent<font style="color: rgb(0, 0, 0);">.</font></div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z4561dd0890f94dbb9b50130cac61e142" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.125</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product-Specific Technology</font>&#8221; means Ionis Product-Specific Know-How and Ionis Product-Specific Patents.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z6f44812eb7184bcabf7eb93468de0f21" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.126</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product Trademarks</font>&#8221; has the meaning set forth in <u>Section 10.10.1(c)</u> (Ownership of Ionis Product Trademarks).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze0338751f5924ae1a56c3bdb0ba08c2f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.127</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Prosecuted Patent Rights</font>&#8221; has the meaning set forth in <u>Section 10.2.1(a)</u> (Right to Prosecute).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z8b66c2f6fa07423cb25e4418eb19f5f0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.128</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Publication</font>&#8221; has the meaning set forth in <u>Section 12.5.2</u> (Ionis&#8217; Right to Publish).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z52ba6a4483924ef38445c26f7abdd65d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.129</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Regulatory Activities</font>&#8221; has the meaning set forth in <u>Section 5.1</u> (Regulatory Responsible Party).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze5ecfdee974a485f96b074e6b4f73b8c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.130</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Technology</font>&#8221; means the Ionis Know-How, the Ionis Patent Rights, and Ionis&#8217; interest in the Joint Collaboration Technology.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z191dbf096a8345b1966b09a1da64dbd4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.131</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Territory</font>&#8221; means worldwide, except for the Otsuka Territory.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z479efd5e9db5435ea1a8f6e1fbb14ba7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.132</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">IRS</font>&#8221; has the meaning set forth in <u>Section 9.10.3</u> (Tax Cooperation).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z90f16f6f46a24b7897e5025408b7ee66" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.133</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration Know-How</font>&#8221; means all Collaboration Know-How that is developed or invented jointly by a Party&#8217;s or its Affiliates&#8217;, licensees&#8217;, Sublicensees&#8217;, or
                      Subcontractors&#8217; employees, agents, or independent contractors, or any Persons contractually required to assign or license such Collaboration Know-How to such Party or any Affiliate of such Party, on the one hand, and the other Party&#8217;s
                      or its Affiliates&#8217;, licensees&#8217;, Sublicensees&#8217;, or Subcontractors&#8217; employees, agents, or independent contractors, or any Persons contractually required to assign or license such Collaboration Know-How to such Party or any Affiliate of
                      such Party, on the other hand.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zd8b5efcd0f26403999f12dff8461c283" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.134</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration Patent Rights</font>&#8221; means all Collaboration Patent Rights that Cover Joint Collaboration Know-How.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="zeefebdbccb6b4711bacb714d51c57af3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.135</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration Technology</font>&#8221; means the Joint Collaboration Know-How and the Joint Collaboration Patent Rights.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z3fb17a5edb7d4d89bc2414e6938b7203" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.136</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">JSCs</font>&#8221; has the meaning set forth in <u>Section 8.2.1</u> (Formation and Purposes of the Joint Steering Committees) and &#8220;<font style="font-weight: bold; font-style: italic;">JSC</font>&#8221; means the Europe JSC or the Asia JSC, as the case may be.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze12ca51c98f54a91a73c52a8f22866fe" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.137</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Know-How</font>&#8221; means proprietary Inventions, discoveries, trade secrets, materials, information, experience, data, formulas, procedures, technology, and results (whether or
                      not patentable), including practices, knowledge, know-how,<font style="font-weight: bold; font-style: italic;">&#160;</font>experience and test data (including physical, chemical, biological, toxicological, pharmacological, clinical and
                      veterinary data), dosage regimens, assays, diagnostics, product specifications, manufacturing techniques and costs, analytical and quality control data and marketing, pricing and distribution costs, and sales practices, methods, data,
                      and descriptions.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z13fb082ff81a46118c4aae3cdc4f0777" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.138</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Knowledge</font>&#8221; means the actual knowledge, without any inquiry or investigation, of (a) with respect to Ionis, its [***]; and (b) with respect to Otsuka, its [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z28696b77cc6243b49a433865e17fe71d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.139</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Licensed Compound</font>&#8221; means the GaINAc-conjugated antisense oligonucleotide compound known as donidalorsen.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf1a25b4850bd48239cfae36c0ce7bab0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.140</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Licensed Product</font>&#8221; means any pharmaceutical product that contains, comprises, or incorporates the Licensed Compound, in all current and future formulations and in any
                      dosage strengths, presentations, or package configuration, and for any mode of administration. For clarity, any combination product comprised of an autoinjector pre-filled with the Licensed Compound is considered a Licensed Product.
                      All products containing or comprising the same Licensed Compound, regardless of the formulation, indication, line extension or otherwise, will be considered the same Licensed Product for all purposes of this Agreement.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zecdbe45275d0461b977cc12cc92a5c10" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.141</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Local Unitary Product Trademark</font>&#8221; has the meaning set forth in <u>Section 10.10.1(a)</u> (Unitary Product Trademarks).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z8b0b8d558e474d6288cef457dd7614c3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.142</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Losses</font>&#8221; has the meaning set forth in <u>Section 13.1</u> (Indemnification by Ionis).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zbb0331fd6e90411eaae27b2f84c4ba8b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.143</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">MAA</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Marketing Authorization Application</font>&#8221; means any (a) New Drug Application as defined in the FD&amp;C
                      Act, (b) a marketing authorization application filed with (i) the EMA under the centralized EMA filing procedure to gain approval to market a biopharmaceutical in the E.U., or (ii) a Regulatory Authority in any country in the E.U. if
                      the centralized EMA filing procedure is not used to gain approval to market a biopharmaceutical in the E.U., or (c) a marketing authorization application filed with the PMDA in Japan, or (d) substantially similar application or
                      submission to those set forth in the foregoing clauses filed with a Regulatory Authority in a country or group of countries to obtain Regulatory Approval to Commercialize a biopharmaceutical or diagnostic product in that country or in
                      that group of countries, in each case ((a) through (d)), including any amendments thereto, and supplemental applications, but excluding Reimbursement Approval applications.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z0d948aaca2314603908f272744dc8075" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.144</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">MAA Acceptance</font>&#8221; means, with respect to a Marketing Authorization Application filed for a Licensed Product, the receipt of written notice of acceptance by the EMA of such
                      Marketing Authorization Application for filing under the centralized filing procedure.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z1504ad54a4954c31b76e34c082c022fa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.145</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***]&#8221; means, [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
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            <table cellspacing="0" cellpadding="0" id="zc4847072148f4ce6a93191bf76380cc0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.146</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***<font style="font-weight: bold; font-style: italic;">]</font>&#8221; means, [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z6c95bf6e6ca6460b9518d72984d7bec1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.147</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacture</font>&#8221; means activities directed to manufacturing, processing, packaging, labeling, filling, finishing, assembly, quality assurance, quality control, testing, and
                      release, shipping, or storage of any pharmaceutical or biologic product (or any components or process steps involving any product or any companion diagnostic), placebo, or comparator agent, as the case may be, including qualification,
                      validation, and scale-up, pre-clinical, clinical, and commercial manufacture and analytic development, product characterization, and stability testing, but excluding activities directed to Development, or Commercialization. &#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing</font>&#8221; and &#8220;<font style="font-weight: bold; font-style: italic;">Manufactured</font>&#8221; will be construed accordingly.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zc774f40730d54c779b31094c1278de3e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.148</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Costs</font>&#8221; means, with respect to a Licensed Product [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zed738e559b914c35a8b42526e10d418c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.149</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Handover Date</font>&#8221; has the meaning set forth in <u>Section 7.1.2</u> (Otsuka Manufacturing).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z448bb28da9894bdaa9ef8844d1c77f06" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.150</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Handover Notice</font>&#8221; has the meaning set forth in <u>Section 7.1.2</u> (Otsuka Manufacturing).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.151</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Technology</font>&#8221; means any or all of (a) methods or materials used in the synthesis or analysis of an oligonucleotide or a Licensed Product regardless of
                      sequence or chemical modification, (b) methods of manufacturing components of an oligonucleotide, and (c) methods or materials used in Manufacturing a Licensed Product.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z73bc6c34984c4d6e80bf174a6606ad36" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.152</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Technology Transfer</font>&#8221; has the meaning set forth in <u>Section 7.4</u> (Manufacturing Technology Transfer).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z71345eaaaf0847879e4d3c28533924dd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.153</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Technology Transfer Agreement</font>&#8221; has the meaning set forth in <u>Section 7.4</u> (Manufacturing Technology Transfer).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="za743ab535c464230ad62fa4b42d5ca83" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.154</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Medical Affairs</font>&#8221; means activities conducted by a Party&#8217;s medical affairs department (or, if a Party does not have a medical affairs department, the equivalent function
                      thereof), including real world evidence, communications with key opinion leaders, continuing medical education, symposia, advisory boards (to the extent related to medical affairs or clinical guidance), activities performed in
                      connection with patient registries, review and approval of materials consistent with a Party&#8217;s or its Affiliate&#8217;s internal SOPs and Applicable Law, interactions and engagements with patient advocacy groups and other key stakeholders,
                      and other similar medical programs and communications.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze3eeac4617fc4e6ca2ce738e66e2a690" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.155</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Milestone Events</font>&#8221; means the Regulatory Milestone Events and the Sales Milestone Events.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf968bf141bbf4f55867d8f3ab143eb75" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.156</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Milestone Payments</font>&#8221; means the Regulatory Milestone Payments and the Sales Milestone Payments.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze4bfe2f0db514316b39ca6c4e7b1cbc5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.157</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 2.7.2(a)</u> (Acquisition of Potential In-Licenses).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze97773883e4240dea7cc6a15abc1e95c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.158</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Net Sales</font>&#8221; means, with respect to any Licensed Product, the amount invoiced by Otsuka or its Affiliates or Sublicensees (each a &#8220;<font style="font-weight: bold; font-style: italic;">Selling Party</font>&#8221;) for sales of such Licensed Product in arm&#8217;s length transactions to Third Parties in all countries in the Otsuka Territory, less deduction (if not already deducted in the amount invoiced)
                      of the following items with respect to sales of such Licensed Product:</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="z2208376f56f44d3ba91efcf40006f6bf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top;">(a)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Normal and customary trade, quantity, or cash discounts to non-affiliated brokers, agents or customers to the extent actually allowed and taken, <font style="font-style: italic;">provided</font> that such discounts are not applied
                      disproportionately to the Licensed Products when compared to the other products of the Selling Party, as applicable;</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z8907e89c35a14070b3b687c44d25c6ce" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top;">(b)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Actual amounts repaid or credited by reason of rejections, returns, defects, price adjustments, billing errors, or trial prescriptions, including amounts repaid, discounted or credited by reason of risk sharing schemes with respect
                      to the Licensed Product with any Governmental Authority;</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zb9d58ae0332c4a969fda4e702acd8025" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top;">(c)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>To the extent separately stated on purchase orders, invoices, or other documents of sale, any taxes, tariffs, duties, excises or other governmental charges (including any value added tax, sales tax, consumption tax or similar tax,
                      other than any taxes based on income) imposed or levied on the production, sale, transportation, delivery, or use, exportation or importation of the Licensed Products;</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z0f3a6bbab6584ce488c6dbb31b452cf2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top;">(d)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Rebates, reimbursements, fees, clawbacks, discounts or<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#160;</sup>chargeback payments paid, granted or credited to managed health care organizations, pharmacy
                      benefit managers (or equivalent thereof), national, state/provincial, local, and other governments or Governmental Authorities, their agencies/purchasers/reimbursement providers (including those requested by any Governmental Authority
                      any time after the actual sale of a Licensed Product), or to any Third Party payor, administrator, contractee or purchaser, including trade customers, including any fees levied by any Governmental Authority as a result of healthcare
                      reform policies, and including those offered as a result of the clinical or real-world performance of the Licensed Product after it is marketed and sold;</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="za838f408e18a47e8b2fa76b8f450b28b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top;">(e)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Outbound transportation costs prepaid or allowed and costs of insurance in transit, with the exclusion of storage and warehousing costs;</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zd56774ec68884ca09d02ed0ff5037aa1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top;">(f)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Any invoiced amounts that are not collected, including bad debts; and</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zcf1ce61a2e3847e5b7d7b7f78d838b0c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top;">(g)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Any other deductions that are consistent with the Selling Party&#8217;s Accounting Standards and are not duplicative of the above deductions;</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div style="text-align: justify; margin-left: 81pt;"><font style="font-style: italic;">provided</font> that the following deductions are not allowed in the calculation of Net Sales: (i) co-payment assistance; (ii) discounts offered to insurers
              to facilitate patient access to the product; (iii) program and data management fees paid to wholesalers/distributors; (iv) commissions paid to third-party logistics (3PL) providers; and (v) product samples shipped to indirect customers.</div>
            <div>&#160;</div>
            <div style="text-align: justify; text-indent: 36pt; margin-left: 45pt;">If a Selling Party makes any adjustments to such deductions after the associated Net Sales have been reported pursuant to this Agreement, then the adjustments will be
              reported and reconciled with the next report and payment of any royalties due.</div>
            <div>&#160;</div>
            <div style="text-align: justify; text-indent: 36pt; margin-left: 45pt;">Net Sales will not include (i) any payments among Selling Parties, unless such paying party is the end user of the relevant Licensed Product, (ii) any payments in
              consideration of supplies of the applicable Licensed Product for use in Clinical Trials, or (iii) payments for promotional samples, compassionate use, named-patient use, or expanded access, indigent or other patient access programs, in each
              case when sold or distributed at or below the applicable Selling Party&#8217;s costs (including supply price paid).</div>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <div style="text-align: justify; text-indent: 36pt; margin-left: 45pt;">If a Selling Party sells a Licensed Product in the Otsuka Territory as part of a therapy or product in combination with other pharmaceutical or biologic products,
              diagnostic products, ingredients, delivery devices or other components other than the Licensed Compound (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Other Product</font>&#8221;) whether combined in a single formulation or
              package, formulated or packaged separately but sold under a single label approved by a Regulatory Authority, packaged together for sale or shipment as a single unit, or marketed or sold collectively as a single product, but, in all cases,
              sold together for a single price (a &#8220;<font style="font-weight: bold; font-style: italic;">Combination Product</font>&#8221;), Net Sales of such Combination Product for the purposes of determining payments based on Net Sales hereunder will be
              calculated by multiplying actual Net Sales of such Combination Product as determined in the first paragraph of this Net Sales definition (&#8220;<font style="font-weight: bold; font-style: italic;">Combination Product Net Sales</font>&#8221;) by the
              fraction A/(A+B) where A is the average selling price of the Licensed Compound sold separately in such country during the applicable reporting period, and B is the sum of the average selling price(s) of the Other Product(s) in the Combination
              Product in such country during the same reporting period. If the Licensed Compound is sold separately in an applicable reporting period in a country in the Otsuka Territory, but the Other Product(s) are not sold separately in the same country
              in the same reporting period, then Net Sales of such Combination Product will be calculated by multiplying the Combination Product Net Sales by the fraction A/C where A is the average selling price of the Licensed Compound sold separately in
              such country during such reporting period, and C is the average selling price of the Combination Product in such country during such reporting period. If neither the Licensed Compound nor the Other Product(s) are sold separately in the same
              country in the same reporting period, then Net Sales of such Combination Product will be calculated by multiplying the Combination Product Net Sales by a fraction that reflects the value of the Licensed Compound relative to the value of the
              Other Product(s) in such Combination Product, which fraction shall be determined by Otsuka in its reasonable judgment, and reasonably acceptable to Ionis, and in such event, Otsuka shall provide Ionis with supporting documentation for such
              determination. Notwithstanding the foregoing, the Parties agree that the Licensed Product Manufactured and supplied by Ionis pursuant to the Supply Agreements in the form of an autoinjector pre-filled with Licensed Compound will not be
              subject to the terms of this paragraph, and such autoinjector will not be deemed an Other Product for purposes of calculating Net Sales.</div>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze76cf9c381af473fb18c921f2ff6ab1b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.159</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***<font style="font-weight: bold; font-style: italic;">]</font>&#8221; has the meaning set forth in <u>Section 4.4.4(a)</u> (Shared Costs).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z54a006a28e4c47ff90c8a997fff6c981" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.160</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***<font style="font-weight: bold; font-style: italic;">]</font>&#8221; has the meaning set forth in <u>Section 4.4.4(a)</u> (Shared Costs).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zdfed58f0a49e48a19a5e2e12fa0b0d78" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.161</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Non-Clinical Asia HAE Development Plan</font>&#8221; has the meaning set forth in <u>Section 4.2.2(b)</u> (Asia Territory).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z51ef0c4e63e0491a80dfe3fc7efa5751" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.162</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Non-Clinical Europe HAE Development Plan</font>&#8221; has the meaning set forth in <u>Section 4.2.2(a)</u> (Europe Territory).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z4d931d6ffdcc4f16a65d139607c086d0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.163</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Non-Clinical HAE Development Plans</font>&#8221; means the Non-Clinical Asia HAE Development Plan and the Non-Clinical Europe HAE Development Plan.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z9e08b2e318f74490851a3fbfb9088fb6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.164</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">OFAC</font>&#8221; means the Office of Foreign Assets Control of the United States Department of the Treasury or any successor agency thereto.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z649b06d9e66843ac8c6d3e52645edb71" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.165</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ongoing Cross-Territory Studies</font>&#8221; has the meaning set forth in <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf1b70b1fceeb4070ab5943fba601dc70" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.166</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Opt-In Fee</font>&#8221; has the meaning set forth in <u>Section 4.4.4(c)</u> (Otsuka Opt-In).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="z8e504a2ee2c04bbb8fb12177b2c1add6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.167</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Opt-In Notice</font>&#8221; has the meaning set forth in <u>Section 4.4.4(c)</u> (Otsuka Opt-In).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z389c855a44b54a4cb322aa825228001d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.168</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Original Agreement</font>&#8221; has the meaning set forth in the Recitals.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z79300b1722514724946a230ac529bea8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.169</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Original Agreement Term</font>&#8221; means the period of time commencing on the Original Effective Date and continuing until the Restatement Date.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zcaa496959914410aa5ca52caebcd1c27" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.170</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Original Effective Date</font>&#8221; has the meaning set forth in the Recitals.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.171</td>
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                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Other Covered Party</font>&#8221; means any political party or party official, or any candidate for political office.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.172</td>
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                    <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 2.7.2(c)</u> ([***] Potential In-Licenses).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.173</td>
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                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Other Product</font>&#8221; has the meaning set forth in <u>Section 1.158</u> of this <u>Appendix 1</u> (Definitions).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.174</td>
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                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Collaboration Know-How</font>&#8221; has the meaning set forth in <u>Section 10.1.2(b)</u> (Ownership of Arising Intellectual Property).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.175</td>
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                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Collaboration Patent Rights</font>&#8221; has the meaning set forth in <u>Section 10.1.2(b)</u> (Ownership of Arising Intellectual Property).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.176</td>
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                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Indemnitee</font>&#8221; has the meaning set forth in <u>Section 13.1</u> (Indemnification by Ionis).</div>
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                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.177</td>
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                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Know-How</font>&#8221; means all Collaboration Know-How (excluding Otsuka&#8217;s interest in Joint Collaboration Know-How) that is (a) Controlled by Otsuka or any of its Affiliates
                      during the Term and (b) necessary or reasonably useful to Exploit a Licensed Product.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.178</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Patent Rights</font>&#8221; means all Collaboration Patent Rights (excluding Otsuka&#8217;s interest in Joint Collaboration Patent Rights) that are (a) Controlled by Otsuka or any of
                      its Affiliates during the Term and (b) necessary or reasonably useful (or, with respect to patent applications, would be necessary or reasonably useful if such patent applications were to issue as patents) to Exploit a Licensed
                      Product.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.179</td>
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                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Product Trademarks</font>&#8221; has the meaning set forth in <u>Section 10.10.1(b)</u> (Ownership of Otsuka Product Trademarks).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.180</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div> &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Publication</font>&#8221; has the meaning set forth in <u>Section 12.5.1</u> (Otsuka&#8217;s Right to Publish).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z5cd85c80c63742608408cbb70e2d0763" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.181</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Technology</font>&#8221; means Otsuka Know-How, Otsuka Patent Rights, and Otsuka&#8217;s interest in the Joint Collaboration Technology.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.182</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory</font>&#8221; means the Asia Territory and the Europe Territory.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z5a437ba102284eb182b28ebb51d22837" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.183</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory Brand Strategy&#8221; </font>has the meaning set forth in <u>Section 6.4.2</u> (Otsuka Territory Brand Strategy and Commercialization Operating Plans).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z53fa8ba24fdc4b49be9654fa3dbc6648" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.184</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory Commercialization Operating Plans</font>&#8221; has the meaning set forth in <u>Section 6.4.2</u> (Otsuka Territory Brand Strategy and Commercialization Operating
                      Plans).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z628391c8d8fb4c9b81f3002d68625e3c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.185</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory Medical Affairs Plans</font>&#8221; has the meaning set forth in <u>Section 6.6.2</u> (Otsuka Territory Medical Affairs Plans).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.186</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory-Specific Development Plans</font>&#8221; has the meaning set forth in <u>Section 4.3.2</u> (Asia Territory-Specific Development Plan).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z3f75fe49a8b148fc8a5ddcd13d28831e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.187</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory Trademark Infringement</font>&#8221; has the meaning set forth in <u>Section 10.10.4(a)</u> (Unitary Product Trademark).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z03e83a59a2444c45b167553b884d35ae" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.188</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Packaging and Labeling</font>&#8221; means primary, secondary, or tertiary packaging and labeling of a Licensed Product (in its commercial packaging presentation) for sale or use in a
                      country, including the Approved Labeling and insertion of materials such as patient inserts, patient medication guides, and professional inserts and any other written, printed, or graphic materials accompanying such Licensed Product
                      and any brand security or anti-counterfeiting measures included in the packaging elements for such Licensed Product considered to be part of the finished packaged Licensed Product, and all testing and release thereof.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z460778a516444bc3aad0368aa21c1214" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.189</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Party Vote</font>&#8221; has the meaning set forth in <u>Section 8.5.1</u> (General Decision-Making Process).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z08752c0f153540e5b4eb16f2ae97c817" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.190</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Patent Challenge</font>&#8221; means, with respect to a Person, that such Person contests or assists a Third Party in contesting the scope, validity, or enforceability of a Patent
                      Right or any foreign counterpart thereof anywhere in the world in any court, tribunal, arbitration proceeding, or other proceeding, including the U.S. Patent and Trademark Office and the U.S. International Trade Commission. A Patent
                      Challenge includes: (a) filing an action under 28 U.S.C. &#167;&#167; 2201-2202 seeking a declaration of invalidity or unenforceability of any such Patent Right; (b) filing, or joining in, a petition under 35 U.S.C. &#167; 311 to institute <font style="font-style: italic;">inter partes</font> review of any such Patent Right; (c) filing, or joining in, a petition under 35 U.S.C. &#167; 321 to institute post-grant review of any such Patent Right or any portion thereof; (d) filing
                      or commencing any opposition, nullity, or similar proceedings challenging the validity of any such Patent Right in the Territory; or (e) any foreign equivalent of clauses (a), (b), (c), or (d), including any proceeding in any country
                      or patent office in any country or region in the Otsuka Territory.</div>
                  </td>
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            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.191</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Patent Prosecution</font>&#8221; means activities directed to (a) preparing, filing, and prosecuting applications (of all types) for any Patent Right, (b) maintaining any Patent
                      Right, and (c) deciding whether to abandon or maintain any Patent Right.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.192</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Patent Rights</font>&#8221; means (a) all patents, patent applications, and utility models in any country or jurisdiction, including provisional applications, priority applications,
                      and international applications, (b) all patent applications filed either from such patents or patent applications or from an application claiming priority from any of these, including divisionals, continuations, and
                      continuations-in-part, (c) any and all patents that have issued or in the future issue from the foregoing patent applications, (d) any and all substitutions, renewals, registrations, confirmations, revalidations, reissues, and
                      re-examinations of the foregoing patents or patent applications, and (e) extensions, restorations, supplemental protection certificates, and the like based on any of the foregoing patents or patent applications.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.193</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Payment Assignment</font>&#8221; has the meaning set forth in <u>Section 16.1</u> (Assignment).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.194</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Payment Forms</font>&#8221; means one copy of each of the following documents which, at the time Ionis provides such documents to Otsuka, must be currently effective (un-expired),
                      completed and signed: the United States Internal Revenue Service Form 6166 (United States Residency Certification) as received from the United States Internal Revenue Service; Form 3 (Application Form for Income Tax Convention); and
                      Form 17 (Attachment Form for Limitation on Benefits Article).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.195</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Person</font>&#8221; means any corporation, limited or general partnership, limited liability company, joint venture, trust, unincorporated association, governmental body, authority,
                      bureau, or agency, or any other entity or body, or an individual.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="ze72e8651f7554705a9df5473bdbff959" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.196</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Pharmacovigilance Agreement</font>&#8221; means an agreement regarding receipt, investigation, and reporting of product complaints, adverse events, product recalls, and any other
                      information related to the safety of the Licensed Products in the Territory.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z076347188da14fc994713acd597834fb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.197</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Phase 3 Clinical Trial</font>&#8221; means a Clinical Trial of a Licensed Product that satisfies the requirements for a Phase 3 study as defined in 21 CFR &#167; 312.21(c) (or any amended
                      or successor regulations) or that satisfies the requirements of similar laws or regulations outside the United States.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z35fb4d7a926e48b9b5752a12a385c00d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.198</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***]&#8221; means the [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z636df2abdaed45679e44886acf20e7bc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.199</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">PMDA</font>&#8221; means the Pharmaceuticals and Medical Devices Agency or any successor agency thereto.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z33950fc5dbb74ee98a40f2c88623badb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.200</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Post-Approval Cross-Territory Mandatory Studies</font>&#8221; has the meaning set forth in <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z96d0ef8647794487b9b1d1944530e3c7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.201</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Post-Approval Mandatory Study</font>&#8221; means any Clinical Trial or other study of a pharmaceutical or biologic product initiated following receipt of Regulatory Approval or to be
                      conducted after receipt of Regulatory Approval, in each case, that was mandated by the applicable Regulatory Authority in any country in the Territory as a condition of receiving or maintaining a Regulatory Approval for a product with
                      respect to a particular indication in such country&#160; (such as post-marketing approval studies and observational studies, if required by any Regulatory Authority in any country in the Territory to support or maintain Regulatory Approval
                      for a product in such country) or that is required for a label extension for a product in such country. For clarity, a [***] is a Post-Approval Mandatory Study.</div>
                  </td>
                </tr>

            </table>
            <br>
            <table cellspacing="0" cellpadding="0" id="zdd0882d3a9124b05925384d78c55737a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.202</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Potential In-License</font>&#8221; has the meaning set forth in <u>Section 2.7.2(a)</u> (Acquisition of Potential In-Licenses).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zdec6a1c28eb24b1f9a0b254859a3b603" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.203</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Product Materials</font>&#8221; has the meaning set forth in <u>Section 6.8</u> (Product Materials).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z92a8f77c57354d0b883eb4798e6355c3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.204</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Product-Specific Patents</font>&#8221; means Patent Rights Controlled by a Party or any of its Affiliates as of or after the Original Effective Date claiming: (a) the composition of
                      matter of a Licensed Product, or (b) methods of using a Licensed Product.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z7d66d596831d476d85b82338bc394989" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.205</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Professional Requirements</font>&#8221; means (a) the codes and standards of the European Accreditation Council for Continuing Medical Education (EACCME) and the European Federation
                      of Pharmaceutical Industries and Associations (EFPIA), (b) the codes of the Prescription Medicines Code of Practice Authority (PMCPA) and the Association of the British Pharmaceutical Industry (ABPI), (c) FDA&#8217;s regulations, guidance,
                      and enforcement letters concerning the advertising of prescription drug products, (d) the American Medical Association&#8217;s Guidelines on Gifts to Physicians from Industry, (e) the Accreditation Council for Continuing Medical Education
                      (ACCME) Standards for Commercial Support of Continuing Medical Education, (f) the Pharmaceutical Supply Chain Initiative (PSCI) and Pharmaceutical Industry Principles for Responsible Supply Chain Management, (g) the Code on
                      Interactions with Healthcare Professionals promulgated by the Pharmaceutical Research and Manufacturers of America (PhRMA Code), (h) the Department of Health and Human Services Office of Inspector General Compliance Program Guidance
                      for Pharmaceutical Manufacturers (OIG Compliance Guidance), and (i) all other accepted national and international pharmaceutical industry codes of practice in and for the relevant countries in the Territory, as any of the foregoing
                      may be amended from time-to-time.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="z4a906aff40c744aaa5c9eeef96693e17" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.206</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Publication</font>&#8221; has the meaning set forth in <u>Section 12.5</u> (Publications).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z31d65e26f2c847eda6946494490dcee5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.207</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">PV Subcommittee</font>&#8221; has the meaning set forth in <u>Section 5.11</u> (Pharmacovigilance Subcommittee).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z44489c3269da46df990cfe2e26907b86" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.208</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***]&#8221; means [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z9b66f222a3c249478773b382a9553d26" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.209</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Quality Agreement</font>&#8221; has the meaning set forth in <u>Section 7.2.3</u> (Quality Agreements).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z1deaf22ce902428fad37e3659859b948" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.210</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Receiving Party</font>&#8221; has the meaning set forth in <u>Section 1.39</u> (Confidential Information) of this <u>Appendix 1</u> (Definitions).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z408ed0e182334076a0f4765355464b45" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.211</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Reduced Royalties</font>&#8221; has the meaning set forth in <u>Section 9.3.3</u> (Reduced Royalty Term).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z469c533df16b479f94f0864f48adb764" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.212</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Reduced Royalty Term</font>&#8221; has the meaning set forth in <u>Section 9.3.3</u> (Reduced Royalty Term).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zd1acccdcc2d3416d8c6289ad22376af8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.213</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 9.3.2(c)</u> ([***]).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zcaa1a998a31f4b3188475eaeec179725" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.214</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Region</font>&#8221; means each of the (a) Asia Territory and (b) the Europe Territory.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z9d70abf5243b4e1bbcff0f80e5207a16" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.215</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Approval</font>&#8221; means, with respect to a particular country or other regulatory jurisdiction, any approval of an MAA or other approval, product, or establishment
                      license, registration, or authorization of any Regulatory Authority necessary for the commercial sale of a pharmaceutical, diagnostic, or biologic product in such country or other regulatory jurisdiction, excluding, in each case,
                      Reimbursement Approval.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z10c30c92f8b64792b74a0e0def005aa6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.216</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Authority</font>&#8221; means, in a particular country or jurisdiction, any applicable Governmental Authority involved in granting Regulatory Approval in such country or
                      jurisdiction, including (a) in the U.S., the FDA and any other applicable Governmental Authority in the U.S. having jurisdiction over any pharmaceutical, diagnostic, or biologic product, (b) in the E.U., the EMA and any other
                      applicable Governmental Authority in the E.U. having jurisdiction over any pharmaceutical, diagnostic, or biologic product, (c) in Japan, the PMDA and any other applicable Governmental Authority in Japan having jurisdiction over any
                      pharmaceutical, diagnostic, or biologic product, and (d) in other countries, other analogous Governmental Authorities having jurisdiction over any pharmaceutical, diagnostic, or biologic product.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zeeb8c23443a34dc68be3adb1eb69c64c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.217</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Exclusivity</font>&#8221; means, with respect to a Licensed Product in a country in the Otsuka Territory, the period of time during which: (a) Otsuka or its Affiliate or
                      Sublicensee has been granted the exclusive legal right by a Regulatory Authority (or is otherwise entitled to the exclusive legal right by operation of Applicable Law) in such country to market and sell such Licensed Product, and such
                      right precludes a Third Party from making such Licensed Product available for purchase for any indication; or (b) the data and information submitted by Otsuka or its Affiliate or Sublicensee to the relevant Regulatory Authority in
                      such country for purposes of obtaining Regulatory Approval of such Licensed Product may not be referenced, or relied upon in any way by a Third Party or such Regulatory Authority to support the Regulatory Approval or marketing of any
                      product by a Third Party in such country, or if such data and information is referenced, or relied upon to support a Regulatory Approval granted to a Third Party in such country, the product may not be placed on the market for any
                      indication.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="zd33bab9ff8d546419a862e0fc4721125" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.218</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Milestone Events</font>&#8221; has the meaning set forth in <u>Section 9.2.1</u> (Regulatory Milestones).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z892993a214a24058a90428a7184c74c3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.219</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Milestone Payments</font>&#8221; has the meaning set forth in <u>Section 9.2.1</u> (Regulatory Milestones).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zae6432439741446298e78ea2b806a59b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.220</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Responsible Party</font>&#8221; means the Party designated under <u>Section 5.1</u> (Regulatory Responsible Party).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z2c32a1d20bad4d84b46be7100a2f545f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.221</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Submission</font>&#8221; means any filing, application, or submission with any Regulatory Authority in support of the Development, Manufacture, Commercialization, or other
                      Exploitation of a pharmaceutical, diagnostic, or biologic product (including to obtain, support, or maintain Regulatory Approval from that Regulatory Authority), and all written or electronic correspondence or communication with or
                      from the relevant Regulatory Authority, as well as minutes of any material meetings, telephone conferences, or discussions with the relevant Regulatory Authority. Regulatory Submissions include all INDs, MAAs, and other applications
                      for Regulatory Approval and their equivalents.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z12f1be7f6730452f8a67ee1a80e4a197" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.222</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Support</font>&#8221; has the meaning set forth in <u>Section 5.6</u> (Cooperation).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zfb08c4daf93c45bfa4a863d68422be41" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.223</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Reimbursed Manufacturing Tech Transfer Costs</font>&#8221; has the meaning set forth in <u>Section 7.4</u> (Manufacturing Technology Transfer).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf4519284a3e049a0b8b3e4217b2370e5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.224</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Reimbursement Approval</font>&#8221; means, as applicable, (a) the Governmental Authority approval, agreement, determination, or other decision establishing prices that can be charged
                      for a product in regulatory jurisdictions where the applicable Governmental Authority approves or determines the prices charged to end-users for pharmaceutical, diagnostic, or biologic products, or (b) the Governmental Authority
                      approval, agreement, determination or decision establishing the prices at which a product will be reimbursed in regulatory jurisdictions where the applicable Governmental Authority approves, determines or recommends the reimbursement
                      or use of pharmaceutical, diagnostic, or biologic products.</div>
                  </td>
                </tr>

            </table>
            <br>
            <table cellspacing="0" cellpadding="0" id="zff91103233ac4523befbb72737cf13a4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.225</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Remedial Action</font>&#8221; has the meaning set forth in <u>Section 5.13.1</u> (Notification and Determination).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z5d6e6509f5b640b08da11d7be3ca24e4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.226</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Representatives</font>&#8221; means, with respect to a Person, such Person&#8217;s employees, officers, directors, consultants, contractors, Subcontractors, and agents, in each case, who
                      are authorized to act on behalf of such Person.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf9d23ddee32c4292846c0a49e855c2d7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.227</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Requested Assistance</font>&#8221; has the meaning set forth in <u>Section 3.2</u> (Technology Transfer Costs).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zb23176135a9d47a98253bb9096611cef" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.228</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Restatement Date</font>&#8221; has the meaning set forth in the Preamble.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z362afc744c964ab2a0cd662a93ee9082" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.229</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Restatement Upfront Payment</font>&#8221; has the meaning set forth in <u>Section 9.1</u> (Upfront Payment).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z7bdee9459c524985b5a6d2d99ab2137d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.230</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Restricted Party</font>&#8221; means any individual or entity on one or more of the Restricted Party Lists.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.231</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Restricted Party List</font>&#8221; means the list of sanctioned entities maintained by the United Nations; the Specially Designated Nationals and Blocked Persons List, the Foreign
                      Sanctions Evaders List and the Sectoral Sanctions Identifications List, all administered by OFAC; the U.S. Denied Persons List, the U.S. Entity List, and the U.S. Unverified List, all administered by the U.S. Department of Commerce;
                      and the entities subject to restrictive measures and the consolidated list of Persons, Groups, and Entities Subject to E.U. Financial Sanctions, as implemented by the E.U. Common Foreign &amp; Security Policy; and similar lists of
                      restricted parties maintained by the Governmental Authorities of the countries that have jurisdiction over the activities conducted under this Agreement.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.232</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Reversion License</font>&#8221; has the meaning set forth in <u>Section 14.9.2(a)</u> (License Grant).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z6d8fd7a87abe4f65a96847faf21f42a8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.233</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Review Period</font>&#8221; has the meaning set forth in <u>Section 12.5.1</u> (Otsuka&#8217;s Right to Publish).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z6f11b692b10c42f695df73cee49b9879" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.234</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">ROFN Exercise Notice</font>&#8221; has the meaning set forth in <u>Section 2.8.1</u> (ROFN Exercise).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z98993cde94e74ec0ae6e3b7ca63ac02f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.235</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">ROFN Negotiation Period</font>&#8221; has the meaning set forth in <u>Section 2.8.2</u> (Negotiation).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z7caeeaef15254e6db65430ceffb6bba1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.236</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">ROFN Notice and Package</font>&#8221; has the meaning set forth in <u>Section 2.8.1</u> (ROFN Exercise).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z53ef39b5d5974415b4761ee281e6e036" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.237</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">ROFN Territory</font>&#8221; has the meaning set forth in <u>Section 2.8.1</u> (ROFN Exercise).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zdf114c689aad49fa98f3d516f229d87b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.238</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Royalties</font>&#8221; has the meaning set forth in <u>Section </u><u>9.3.3</u> (Reduced Royalty Term).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.239</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Royalty Report</font>&#8221; has the meaning set forth in <u>Section </u><u>9.3.4(b)</u> (Royalty Report).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z9efca0c169814a50a274abcec77af076" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.240</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Royalty Term</font>&#8221; has the meaning set forth in <u>Section </u><u>9.3.3</u> (Reduced Royalty Term).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zbc3bec43df404601962212c6109f7e06" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.241</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 9.3.1</u> (Royalty Payments During the Initial Royalty Term).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z38f6d882711e4b9780e578fe03b4468e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.242</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Rules</font>&#8221; has the meaning set forth in <u>Section 15.2.2</u> (Arbitration).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z4929ed7e63d847ca9f8abaa6b17bee99" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.243</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Sales Milestone Events</font>&#8221; has the meaning set forth in <u>Section </u><u>9.2.2</u> (Sales Milestones).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z0fa4942522a648d4a006f37877045223" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.244</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Sales Milestone Payments</font>&#8221; has the meaning set forth in <u>Section </u><u>9.2.2</u> (Sales Milestones).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z941e343f94eb41328b72ad0f3c8fac89" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.245</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Selling Party</font>&#8221; has the meaning set forth in <u>Section 1.158</u> of this <u>Appendix 1</u> (Definitions).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z948b528a2466475a99f726c08dd00076" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.246</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***<font style="font-weight: bold; font-style: italic;">]</font>&#8221; has the meaning [set forth in <u>Section 4.4.1(c)</u> (Shared Development Costs)].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zdb4fb30e918449fd97cb28ff1f5c3ed6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.247</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Shared Cross-Territory Development Costs</font>&#8221; has the meaning set forth in <u>Section 4.4.1(c)</u> (Shared Development Costs).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z807644270afc453d88dfaf1bc087f6e4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.248</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Shared Development Budget</font>&#8221; has the meaning set forth in <u>Section 4.4.2(a)</u> (Shared Development Budget).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z8b22c102f53944cea2fc7e8ca53cb611" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.249</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Subcommittee</font>&#8221; has the meaning set forth in <u>Section 8.3.1</u> (Formation; Authority).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zae3066f438524d118faae8f87edc3978" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.250</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Subcommittee Co-Chairperson</font>&#8221; has the meaning set forth in <u>Section 8.3.2</u> (Subcommittee Leadership and Meetings).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf30b8ff8dde94c42930598bb4a4ceccf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.251</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Subcontractors</font>&#8221; has the meaning set forth in <u>Section 2.3.2</u> (Right to Subcontract).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
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            <table cellspacing="0" cellpadding="0" id="zb29966c92580404ab9b79e9e0fe8263e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.252</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Sublicensee</font>&#8221; means, with respect to a Party, any Third Party to which such Party or its Affiliate grants a sublicense under any of the rights licensed to the applicable
                      Party under this Agreement other than a Subcontractor.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z71e442660bad4941a63255e3afce0f10" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.253</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Supply Agreements</font>&#8221; has the meaning set forth in <u>Section 7.2.2</u> (Commercial Supply Agreement).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z15500635a73d4a40a5e32205b02a7889" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.254</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Tax</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Taxes</font>&#8221; means any present or future taxes, levies, imposts, duties, charges, assessments or fees of
                      any nature (including any interest thereon), including value add, sales, excise or similar taxes.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z799283307c5f42619774432736fcb7df" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.255</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Technology Transfer</font>&#8221; has the meaning set forth in <u>Section 3.1</u> (Initial Know-How Transfer).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z0d1b2be6505c451c92ad6b0178552893" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.256</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Term</font>&#8221; has the meaning set forth in <u>Section 14.1</u> (Term).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z99f8e9d36efd408487ca007ddf4d3732" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.257</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Terminated Region</font>&#8221; means (a) any Region pursuant to which the non-breaching Party terminates this Agreement pursuant to <u>Section 14.2</u> (Termination for Material
                      Breach), (b) the Europe Territory, the Asia Territory, or any country other than Japan in the Asia Territory, in each case, for which Otsuka terminates this Agreement pursuant to <u>Section 14.3</u> (Termination by Otsuka for
                      Convenience), or (c) all countries in the Territory if either Party terminates this Agreement in its entirety pursuant to <u>Section 14.2</u> (Termination for Material Breach), <u>Section 14.4</u> (Discontinuation of Development and
                      Commercialization), <u>Section 14.5</u> (Termination for Patent Challenge), or <u>Section 14.6</u> (Termination for Insolvency).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z8e9718d12d324bc0849da4f4570ae7bb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.258</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Territory</font>&#8221; means (a) the Otsuka Territory, with respect to Otsuka, (b) the Ionis Territory, with respect to Ionis, and (c) collectively, worldwide.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z7d46d028a66d46dfb14b75c32da908bb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.259</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Third Party</font>&#8221; means any Person other than a Party or its Affiliates.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zea0c150bdf2a4aaaa059d6e87c3aa292" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.260</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Claims</font>&#8221; has the meaning set forth in <u>Section 13.1</u> (Indemnification by Ionis).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z2d7cd3224bad442b839df1d4d7aed985" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.261</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 2.8.2</u> (Negotiation).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zeb026681b7b343808e06104b3991d33f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.262</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Patent Challenge</font>&#8221; has the meaning set forth in <u>Section 10.4</u> (Defense of Third Party Patent Challenges).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zcb38e07b433145a6a6309ac1b316ae12" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.263</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Payments</font>&#8221; means, with respect to a Licensed Product, any (a) payments (including upfront payments, milestone payments, license fees, royalties and monetary
                      damages) made by Otsuka or its Affiliate to a Third Party (i) pursuant to an agreement between Otsuka or its Affiliate and such Third Party entered into following the Original Effective Date in accordance with <u>Section 2.7.2</u>
                      (Potential In-Licenses) to obtain rights to Patent Rights or Know-How from such Third Party that would be infringed or misappropriated by the Exploitation of a Licensed Product in the Otsuka Territory or (ii) pursuant to an agreement
                      between Otsuka or its Affiliate and such Third Party, or otherwise, as part of a settlement or to satisfy a judgment in accordance with <u>Section 10.5.3</u> (Settlement), or (b) amounts for which Otsuka reimburses Ionis under a
                      Collaboration In-License, in each case ((a) or (b)), that are directly in consideration for or reasonably allocable to a license or sublicense (as applicable) to Otsuka or its Affiliate under, or are paid in settlement or to satisfy a
                      judgment of a claim relating to, Patent Rights or Know-How Controlled by such Third Party that would, but for a license thereunder, be infringed or misappropriated by the Exploitation of such Licensed Product.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            </div>
            <table cellspacing="0" cellpadding="0" id="zadb27d7b3034442badf55ec7e661fda1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.264</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Trademark</font>&#8221; means any word, name, symbol, color, shape, designation or any combination thereof, including any trademark, service mark, trade name, brand name, sub-brand
                      name, domain name, trade dress, product configuration, program name, delivery form name, certification mark, collective mark, logo, tagline, slogan, design or business symbol, that functions as an identifier of source or origin,
                      whether or not registered and all statutory and common law rights therein and all registrations and applications therefor, together with all goodwill associated with, or symbolized by, any of the foregoing.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="za82267df55f64b6eb6e543a3e7612e61" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.265</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Trademark Infringement Suit</font>&#8221; has the meaning set forth in <u>Section 10.10.5(a)</u> (Unitary Product Trademarks).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z261da34268d745c8af615aa6fe91ce14" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.266</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Transition Plan</font>&#8221; has the meaning set forth in <u>Section 14.9.3(a)</u> (Scope).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zdeb3469a96574d978defec868ceaa909" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.267</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Transition Services</font>&#8221; has the meaning set forth in <u>Section 14.9.3(a)</u> (Scope).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zce4ba9e3d1114afe96d395fb87bbfeeb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.268</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Unitary Product Trademark</font>&#8221; has the meaning set forth in <u>Section 10.10.1(a)</u> (Unitary Product Trademarks).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zf01e32c2a5574d2daf6eaabb19cd36e5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.269</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">U.S.</font>&#8221; means the United States of America (including all possessions and territories thereof, including Puerto Rico).</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="zd98846fa5fd1447eadd629e1ac7e6a30" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.270</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">U.S. Dollars</font>&#8221; or &#8220;<font style="font-weight: bold;">$</font>&#8221; means the legal tender of the U.S.</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z10847ad0d0d047438935a5b04431210d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.271</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Valid Claim</font>&#8221; means a claim of an issued and unexpired patent (as may be adjusted through a patent term adjustment or extended through supplementary protection certificate
                      or patent term extension or the like) that has not been revoked, held invalid, or held unenforceable by a patent office or other Governmental Authority of competent jurisdiction in a final and non-appealable judgment (or judgment from
                      which no appeal was taken within the allowable time period), and [***].</div>
                  </td>
                </tr>

            </table>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" id="z759c2860d9524d5da157921065dc539f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.272</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>&#8220;<font style="font-weight: bold; font-style: italic;">Withheld Amount</font>&#8221; has the meaning set forth in <u>Section 9.10.2</u> (Withholding Tax).</div>
                  </td>
                </tr>

            </table>
            <div> <br>
            </div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
            </div>
            <div style="font-variant: small-caps; font-weight: bold; font-style: italic;">CONFIDENTIAL</div>
            <u> </u>
            <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 1.69</u></div>
            <div>&#160;</div>
            <div style="text-align: center; font-weight: bold;">Existing Third-Party IP Agreements</div>
            <div>&#160;</div>
            <div style="text-align: justify;">[***]</div>
            <div style="text-align: justify;"> <br>
            </div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
            </div>
            <div style="text-align: center; font-weight: bold;">
              <div style="text-align: justify; font-style: italic; font-weight: bold;">CONFIDENTIAL</div>
            </div>
            <div style="text-align: center; font-weight: bold;">
              <div><u></u><br>
              </div>
            </div>
            <div style="text-align: center; font-weight: bold;">
              <div style="font-variant: small-caps; font-weight: bold;"><u>Schedule </u><u>1.111</u></div>
              <div>&#160;</div>
            </div>
            <div style="text-align: center; font-weight: bold;">Ionis Core Technology Patents</div>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" border="0" id="z1162957d2f054c5b88c736f412252670" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 19.26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center; font-weight: bold;">Ionis File No.</div>
                  </td>
                  <td style="width: 14.82%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center; font-weight: bold;">Country/Treaty</div>
                  </td>
                  <td style="width: 17.58%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center; font-weight: bold;">Application No./</div>
                    <div style="text-align: center; font-weight: bold;">Patent No.</div>
                  </td>
                  <td style="width: 12.72%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center; font-weight: bold;">Filing Date</div>
                  </td>
                  <td style="width: 13.12%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center; font-weight: bold;">Grant Date</div>
                  </td>
                  <td style="width: 22%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center; font-weight: bold;">Title</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 19.26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 14.82%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 17.58%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 12.72%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 13.12%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 22%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 19.26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 14.82%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 17.58%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 12.72%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 13.12%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 22%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 19.26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 14.82%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 17.58%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 12.72%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 13.12%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 22%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 19.26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 14.82%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 17.58%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 12.72%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 13.12%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
                  <td style="width: 22%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 19.26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 14.82%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 17.58%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 12.72%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 13.12%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
                  <td style="width: 22%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 19.26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 14.82%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 17.58%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 12.72%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 13.12%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
                  <td style="width: 22%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 19.26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 14.82%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 17.58%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 12.72%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 13.12%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
                  <td style="width: 22%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 19.26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 14.82%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 17.58%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 12.72%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 13.12%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 22%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 19.26%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 14.82%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 17.58%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 12.72%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
                    <div style="text-align: center;">[***]</div>
                  </td>
                  <td style="width: 13.12%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">&#160;</td>
                  <td style="width: 22%; vertical-align: middle; border-top: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                  <td style="width: 22%; vertical-align: middle; border-color: rgb(0, 0, 0); border-style: solid; border-width: 2px;">
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            </table>
            <div style="text-align: justify;"><font style="font-weight: bold; font-style: italic;"> </font><br>
            </div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
            </div>
            <div>
              <div style="text-align: justify; font-style: italic; font-weight: bold;">CONFIDENTIAL</div>
            </div>
            <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 1.117</u></div>
            <div>&#160;</div>
            <div style="text-align: center; font-weight: bold;">Ionis Manufacturing and Analytical Patents</div>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" border="0" id="z72441ab1723a4c4797b48f28146ebe49" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 18.76%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Ionis File No.</div>
                  </td>
                  <td style="width: 19.53%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Country</div>
                  </td>
                  <td style="width: 13.28%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Application No./</div>
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Patent No.</div>
                  </td>
                  <td style="width: 12.5%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Filing Date</div>
                  </td>
                  <td style="width: 10.94%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Grant Date</div>
                  </td>
                  <td style="width: 25%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Title</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 18.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 19.53%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 13.28%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.5%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 10.94%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 25%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 18.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 19.53%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 13.28%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.5%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 10.94%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 25%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 18.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 19.53%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 13.28%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.5%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 10.94%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 25%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td style="width: 18.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 19.53%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 13.28%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
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                    <div style="margin-left: 9pt; text-indent: -9pt;">&#160;</div>
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                    <div style="margin-left: 9pt; text-indent: -9pt;">&#160;</div>
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                    <div style="margin-left: 9pt; text-indent: -9pt;">&#160;</div>
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                    <div style="margin-left: 9pt; text-indent: -9pt;">&#160;</div>
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                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 10.94%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                    <div style="margin-left: 9pt; text-indent: -9pt;">&#160;</div>
                  </td>
                  <td style="width: 25%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
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                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
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                    <div style="margin-left: 9pt; text-indent: -9pt;">&#160;</div>
                  </td>
                  <td style="width: 25%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 18.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 19.53%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 13.28%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
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                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
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                    <div style="margin-left: 9pt; text-indent: -9pt;">&#160;</div>
                  </td>
                  <td style="width: 25%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 18.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 19.53%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
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                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.5%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 10.94%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                    <div style="margin-left: 9pt; text-indent: -9pt;">&#160;</div>
                  </td>
                  <td style="width: 25%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                </tr>

            </table>
            <div><br>
            </div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
                <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
            </div>
            <div>
              <div style="text-align: justify; font-style: italic; font-weight: bold;">CONFIDENTIAL</div>
            </div>
            <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u> <br>
              </u></div>
            <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 1.124</u></div>
            <div>&#160;</div>
            <div style="text-align: center; font-weight: bold;">Ionis Product-Specific Patents</div>
            <div>&#160;</div>
            <table cellspacing="0" cellpadding="0" border="0" id="z73857a58b0b5429394e760d9664f393b" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 15.48%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Ionis File No.</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Country/</div>
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Treaty</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Status</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Application No./</div>
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Patent No.</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Filing Date</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Grant Date</div>
                  </td>
                  <td style="width: 23.69%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0) rgb(0, 0, 0) rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; font-weight: bold; text-indent: -9pt;">Title</div>
                  </td>
                </tr>
                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                </tr>
                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
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                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
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                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
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                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
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                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                <tr>
                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 16.76%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
                  </td>
                  <td nowrap="nowrap" style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                    <div style="text-align: center; margin-left: 9pt; text-indent: -9pt;">[***]</div>
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                  <td nowrap="nowrap" style="width: 15.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
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              <div style="text-align: justify; font-style: italic; font-weight: bold;">CONFIDENTIAL</div>
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            <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u><br>
                Schedule 4.2.1</u></div>
            <div>&#160;</div>
            <div style="text-align: center; font-weight: bold;">Cross-Territory Clinical Development Plan</div>
            <div>&#160;</div>
            <div style="text-align: center;">[***]</div>
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            </div>
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              <div class="BRPFPageBreak" style="page-break-after: always;">
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              <div style="text-align: justify; font-style: italic; font-weight: bold;">CONFIDENTIAL</div>
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            <div style="text-align: center; font-weight: bold;"><font style="font-variant: small-caps;"><u> <br>
                </u></font></div>
            <div style="text-align: center; font-weight: bold;"><font style="font-variant: small-caps;"><u>Schedule</u></font><u> 4.2.2</u></div>
            <div><br>
            </div>
            <div style="text-align: center; font-weight: bold;">Non-Clinical Europe HAE Development Plan</div>
            <div>&#160;</div>
            <div style="text-align: center;">[***]</div>
            <div><br>
            </div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
              <div class="BRPFPageBreak" style="page-break-after: always;">
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              <div style="text-align: justify; font-style: italic; font-weight: bold;">CONFIDENTIAL</div>
            </div>
            <div style="text-align: center; font-weight: bold;"><font style="font-variant: small-caps;"><u> <br>
                </u></font></div>
            <div style="text-align: center; font-weight: bold;"><font style="font-variant: small-caps;"><u>&#160;Schedule</u></font><u> 4.4.2</u></div>
            <div><br>
            </div>
            <div style="text-align: center; font-weight: bold;">Shared Development Budget</div>
            <div>&#160;</div>
            <div style="text-align: center;">[***]</div>
            <div style="text-align: center;"> <br>
            </div>
            <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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            <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 14.9.3</u></div>
            <div>&#160;</div>
            <div style="text-align: center; font-weight: bold;">Transition Services</div>
            <div>&#160;</div>
            <div style="text-align: center;">[***]</div>
            <div style="text-align: center;"> <br>
            </div>
            <div style="text-align: center;"> <br>
            </div>
            <div style="text-align: center;"> </div>
            <div style="text-align: center;">
              <hr noshade="noshade" align="center" style="height: 2px; color: #000000; background-color: #000000; margin-left: auto; margin-right: auto; border: none;"> </div>
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<DOCUMENT>
<TYPE>EX-31.1
<SEQUENCE>4
<FILENAME>ex31-1.htm
<DESCRIPTION>EXHIBIT 31.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals, Inc.
         Document created using Broadridge PROfile 24.6.1.5240
         Copyright 1995 - 2024 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:956881ca-11d1-4726-85b7-68a37548513a"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><font style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">I, Brett P. Monia, certify that:</div><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" id="z6aee0982a2ca4ddca246ec5f0d8aff80"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; 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;">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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="za90a7366f74a43928499044852ab97c5"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; 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;">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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z0ee6c163a23742928ea9bbb17ab108c6"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; 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;">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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zab9290fbd870474ab6656fc0587af10d"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; 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;">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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z8bde646c9e0b4dc7a468ff9183832418"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; 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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z5fad6e6f50084fc8a061f5e6a6232dd3"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">b)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; 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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z7c55175b49c3436ba80d989e1e3daa25"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">c)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; 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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zbfcf8d60218e49ab865897d5a8237ca6"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">d)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; 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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zdd3f805eb354459aa9fb6c988d921f07"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; 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;">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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z24ec61106a204219be564cd8e6af8975"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; 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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zbd11d28b6f9848c4b550746c7cf2d188"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">b)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; 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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zcb6a87bef85c459bb1f6a9ca75ab9814"><tr><td style="width: 27.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dated: August 1, 2024</div></td><td style="width: 72.41%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 72.41%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; 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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ BRETT P. MONIA</div></td><td style="width: 72.41%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia, Ph.D.</div></td><td style="width: 72.41%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Chief Executive Officer</div></td><td style="width: 72.41%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr></table><div><br></div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; 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>5
<FILENAME>ex31-2.htm
<DESCRIPTION>EXHIBIT 31.2
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals, Inc.
         Document created using Broadridge PROfile 24.6.1.5240
         Copyright 1995 - 2024 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:9770b480-fdae-48ad-8dab-7c414e81bcac"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><font style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">I, Elizabeth L. Hougen, certify that:</div><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" id="z3d945ed45ad34d1fa271ffdc7af8a6ee"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; 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;">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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc64861ee8cfa44109f0288afe468ca7e"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; 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;">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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zf262509b61c3442db710cb9e0b9eacc5"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; 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;">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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z23c599ced3a94e469458369736d10c01"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; 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;">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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z16af1c23172e4acc93512c23afcc24e3"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; 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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z9b84ff2c65ae430495b7773b06ec300a"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">b)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; 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', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="ze9cde339e65b44c6b399e3d6e89c50a0"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">c)</td><td style="width: auto; 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<TYPE>EX-101.LAB
<SEQUENCE>10
<FILENAME>ions-20240630_lab.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by Broadridge PROfile 24.6.1.5240 Broadridge-->
<link:linkbase xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xbrli="http://www.xbrl.org/2003/instance">
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/netLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/net-2009-12-16.xsd#netLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedTotalLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedTotalLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedNetLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedNetLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedTerseLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedPeriodEndLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedPeriodEndLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedPeriodStartLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedPeriodStartLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedLabel" />
  <link:labelLink xlink:type="extended" xlink:role="http://www.xbrl.org/2003/role/link">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_IndividualAxis" xlink:label="IndividualAxis" xlink:title="IndividualAxis" />
    <link:label xlink:type="resource" xlink:label="ecd_IndividualAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_IndividualAxis" xml:lang="en-US" id="ecd_IndividualAxis">Individual [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IndividualAxis" xlink:to="ecd_IndividualAxis" xlink:title="label: IndividualAxis to ecd_IndividualAxis" />
    <link:label xlink:type="resource" xlink:label="ecd_IndividualAxis1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_IndividualAxis1" xml:lang="en-US" id="ecd_IndividualAxis1">Individual:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IndividualAxis" xlink:to="ecd_IndividualAxis1" xlink:title="label: IndividualAxis to ecd_IndividualAxis1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_AllIndividualsMember" xlink:label="AllIndividualsMember" xlink:title="AllIndividualsMember" />
    <link:label xlink:type="resource" xlink:label="ecd_AllIndividualsMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_AllIndividualsMember" xml:lang="en-US" id="ecd_AllIndividualsMember">All Individuals [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AllIndividualsMember" xlink:to="ecd_AllIndividualsMember" xlink:title="label: AllIndividualsMember to ecd_AllIndividualsMember" />
    <link:label xlink:type="resource" xlink:label="ecd_AllIndividualsMember1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_AllIndividualsMember1" xml:lang="en-US" id="ecd_AllIndividualsMember1">All Individuals</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AllIndividualsMember" xlink:to="ecd_AllIndividualsMember1" xlink:title="label: AllIndividualsMember to ecd_AllIndividualsMember1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_InsiderTradingArrLineItems" xlink:label="InsiderTradingArrLineItems" xlink:title="InsiderTradingArrLineItems" />
    <link:label xlink:type="resource" xlink:label="ecd_InsiderTradingArrLineItems" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_InsiderTradingArrLineItems" xml:lang="en-US" id="ecd_InsiderTradingArrLineItems">Insider Trading Arrangements [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InsiderTradingArrLineItems" xlink:to="ecd_InsiderTradingArrLineItems" xlink:title="label: InsiderTradingArrLineItems to ecd_InsiderTradingArrLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_Rule10b51ArrAdoptedFlag" xlink:label="Rule10b51ArrAdoptedFlag" xlink:title="Rule10b51ArrAdoptedFlag" />
    <link:label xlink:type="resource" xlink:label="ecd_Rule10b51ArrAdoptedFlag" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_Rule10b51ArrAdoptedFlag" xml:lang="en-US" id="ecd_Rule10b51ArrAdoptedFlag">Rule 10b5-1 Arrangement Adopted</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Rule10b51ArrAdoptedFlag" xlink:to="ecd_Rule10b51ArrAdoptedFlag" xlink:title="label: Rule10b51ArrAdoptedFlag to ecd_Rule10b51ArrAdoptedFlag" />
    <link:label xlink:type="resource" xlink:label="ecd_Rule10b51ArrAdoptedFlag_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_Rule10b51ArrAdoptedFlag_lbl1" xml:lang="en-US" id="ecd_Rule10b51ArrAdoptedFlag_lbl1">Rule 10b5-1 Arrangement Adopted [Flag]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Rule10b51ArrAdoptedFlag" xlink:to="ecd_Rule10b51ArrAdoptedFlag_lbl1" xlink:title="label: Rule10b51ArrAdoptedFlag to ecd_Rule10b51ArrAdoptedFlag_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_Rule10b51ArrTrmntdFlag" xlink:label="Rule10b51ArrTrmntdFlag" xlink:title="Rule10b51ArrTrmntdFlag" />
    <link:label xlink:type="resource" xlink:label="ecd_Rule10b51ArrTrmntdFlag" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_Rule10b51ArrTrmntdFlag" xml:lang="en-US" id="ecd_Rule10b51ArrTrmntdFlag">Rule 10b5-1 Arrangement Terminated</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Rule10b51ArrTrmntdFlag" xlink:to="ecd_Rule10b51ArrTrmntdFlag" xlink:title="label: Rule10b51ArrTrmntdFlag to ecd_Rule10b51ArrTrmntdFlag" />
    <link:label xlink:type="resource" xlink:label="ecd_Rule10b51ArrTrmntdFlag_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_Rule10b51ArrTrmntdFlag_lbl1" xml:lang="en-US" id="ecd_Rule10b51ArrTrmntdFlag_lbl1">Rule 10b5-1 Arrangement Terminated [Flag]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Rule10b51ArrTrmntdFlag" xlink:to="ecd_Rule10b51ArrTrmntdFlag_lbl1" xlink:title="label: Rule10b51ArrTrmntdFlag to ecd_Rule10b51ArrTrmntdFlag_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_NonRule10b51ArrAdoptedFlag" xlink:label="NonRule10b51ArrAdoptedFlag" xlink:title="NonRule10b51ArrAdoptedFlag" />
    <link:label xlink:type="resource" xlink:label="ecd_NonRule10b51ArrAdoptedFlag" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_NonRule10b51ArrAdoptedFlag" xml:lang="en-US" id="ecd_NonRule10b51ArrAdoptedFlag">Non-Rule 10b5-1 Arrangement Adopted</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonRule10b51ArrAdoptedFlag" xlink:to="ecd_NonRule10b51ArrAdoptedFlag" xlink:title="label: NonRule10b51ArrAdoptedFlag to ecd_NonRule10b51ArrAdoptedFlag" />
    <link:label xlink:type="resource" xlink:label="ecd_NonRule10b51ArrAdoptedFlag_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_NonRule10b51ArrAdoptedFlag_lbl1" xml:lang="en-US" id="ecd_NonRule10b51ArrAdoptedFlag_lbl1">Non-Rule 10b5-1 Arrangement Adopted [Flag]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonRule10b51ArrAdoptedFlag" xlink:to="ecd_NonRule10b51ArrAdoptedFlag_lbl1" xlink:title="label: NonRule10b51ArrAdoptedFlag to ecd_NonRule10b51ArrAdoptedFlag_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_NonRule10b51ArrTrmntdFlag" xlink:label="NonRule10b51ArrTrmntdFlag" xlink:title="NonRule10b51ArrTrmntdFlag" />
    <link:label xlink:type="resource" xlink:label="ecd_NonRule10b51ArrTrmntdFlag" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_NonRule10b51ArrTrmntdFlag" xml:lang="en-US" id="ecd_NonRule10b51ArrTrmntdFlag">Non-Rule 10b5-1 Arrangement Terminated</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonRule10b51ArrTrmntdFlag" xlink:to="ecd_NonRule10b51ArrTrmntdFlag" xlink:title="label: NonRule10b51ArrTrmntdFlag to ecd_NonRule10b51ArrTrmntdFlag" />
    <link:label xlink:type="resource" xlink:label="ecd_NonRule10b51ArrTrmntdFlag_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_NonRule10b51ArrTrmntdFlag_lbl1" xml:lang="en-US" id="ecd_NonRule10b51ArrTrmntdFlag_lbl1">Non-Rule 10b5-1 Arrangement Terminated [Flag]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonRule10b51ArrTrmntdFlag" xlink:to="ecd_NonRule10b51ArrTrmntdFlag_lbl1" xlink:title="label: NonRule10b51ArrTrmntdFlag to ecd_NonRule10b51ArrTrmntdFlag_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_MtrlTermsOfTrdArrTextBlock" xlink:label="MtrlTermsOfTrdArrTextBlock" xlink:title="MtrlTermsOfTrdArrTextBlock" />
    <link:label xlink:type="resource" xlink:label="ecd_MtrlTermsOfTrdArrTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_MtrlTermsOfTrdArrTextBlock" xml:lang="en-US" id="ecd_MtrlTermsOfTrdArrTextBlock">Material Terms of Trading Arrangement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MtrlTermsOfTrdArrTextBlock" xlink:to="ecd_MtrlTermsOfTrdArrTextBlock" xlink:title="label: MtrlTermsOfTrdArrTextBlock to ecd_MtrlTermsOfTrdArrTextBlock" />
    <link:label xlink:type="resource" xlink:label="ecd_MtrlTermsOfTrdArrTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_MtrlTermsOfTrdArrTextBlock_lbl1" xml:lang="en-US" id="ecd_MtrlTermsOfTrdArrTextBlock_lbl1">Material Terms of Trading Arrangement [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MtrlTermsOfTrdArrTextBlock" xlink:to="ecd_MtrlTermsOfTrdArrTextBlock_lbl1" xlink:title="label: MtrlTermsOfTrdArrTextBlock to ecd_MtrlTermsOfTrdArrTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TradingArrByIndTable" xlink:label="TradingArrByIndTable" xlink:title="TradingArrByIndTable" />
    <link:label xlink:type="resource" xlink:label="ecd_TradingArrByIndTable" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_TradingArrByIndTable" xml:lang="en-US" id="ecd_TradingArrByIndTable">Trading Arrangements, by Individual</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TradingArrByIndTable" xlink:to="ecd_TradingArrByIndTable" xlink:title="label: TradingArrByIndTable to ecd_TradingArrByIndTable" />
    <link:label xlink:type="resource" xlink:label="ecd_TradingArrByIndTable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_TradingArrByIndTable_lbl1" xml:lang="en-US" id="ecd_TradingArrByIndTable_lbl1">Trading Arrangements, by Individual [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TradingArrByIndTable" xlink:to="ecd_TradingArrByIndTable_lbl1" xlink:title="label: TradingArrByIndTable to ecd_TradingArrByIndTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TrdArrIndName" xlink:label="TrdArrIndName" xlink:title="TrdArrIndName" />
    <link:label xlink:type="resource" xlink:label="ecd_TrdArrIndName" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_TrdArrIndName" xml:lang="en-US" id="ecd_TrdArrIndName">Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TrdArrIndName" xlink:to="ecd_TrdArrIndName" xlink:title="label: TrdArrIndName to ecd_TrdArrIndName" />
    <link:label xlink:type="resource" xlink:label="ecd_TrdArrIndName_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_TrdArrIndName_lbl1" xml:lang="en-US" id="ecd_TrdArrIndName_lbl1">Trading Arrangement, Individual Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TrdArrIndName" xlink:to="ecd_TrdArrIndName_lbl1" xlink:title="label: TrdArrIndName to ecd_TrdArrIndName_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TrdArrIndTitle" xlink:label="TrdArrIndTitle" xlink:title="TrdArrIndTitle" />
    <link:label xlink:type="resource" xlink:label="ecd_TrdArrIndTitle" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_TrdArrIndTitle" xml:lang="en-US" id="ecd_TrdArrIndTitle">Title</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TrdArrIndTitle" xlink:to="ecd_TrdArrIndTitle" xlink:title="label: TrdArrIndTitle to ecd_TrdArrIndTitle" />
    <link:label xlink:type="resource" xlink:label="ecd_TrdArrIndTitle_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_TrdArrIndTitle_lbl1" xml:lang="en-US" id="ecd_TrdArrIndTitle_lbl1">Trading Arrangement, Individual Title</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TrdArrIndTitle" xlink:to="ecd_TrdArrIndTitle_lbl1" xlink:title="label: TrdArrIndTitle to ecd_TrdArrIndTitle_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TrdArrAdoptionDate" xlink:label="TrdArrAdoptionDate" xlink:title="TrdArrAdoptionDate" />
    <link:label xlink:type="resource" xlink:label="ecd_TrdArrAdoptionDate" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_TrdArrAdoptionDate" xml:lang="en-US" id="ecd_TrdArrAdoptionDate">Adoption Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TrdArrAdoptionDate" xlink:to="ecd_TrdArrAdoptionDate" xlink:title="label: TrdArrAdoptionDate to ecd_TrdArrAdoptionDate" />
    <link:label xlink:type="resource" xlink:label="ecd_TrdArrAdoptionDate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_TrdArrAdoptionDate_lbl1" xml:lang="en-US" id="ecd_TrdArrAdoptionDate_lbl1">Trading Arrangement Adoption Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TrdArrAdoptionDate" xlink:to="ecd_TrdArrAdoptionDate_lbl1" xlink:title="label: TrdArrAdoptionDate to ecd_TrdArrAdoptionDate_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TrdArrTerminationDate" xlink:label="TrdArrTerminationDate" xlink:title="TrdArrTerminationDate" />
    <link:label xlink:type="resource" xlink:label="ecd_TrdArrTerminationDate" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_TrdArrTerminationDate" xml:lang="en-US" id="ecd_TrdArrTerminationDate">Termination Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TrdArrTerminationDate" xlink:to="ecd_TrdArrTerminationDate" xlink:title="label: TrdArrTerminationDate to ecd_TrdArrTerminationDate" />
    <link:label xlink:type="resource" xlink:label="ecd_TrdArrTerminationDate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_TrdArrTerminationDate_lbl1" xml:lang="en-US" id="ecd_TrdArrTerminationDate_lbl1">Trading Arrangement Termination Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TrdArrTerminationDate" xlink:to="ecd_TrdArrTerminationDate_lbl1" xlink:title="label: TrdArrTerminationDate to ecd_TrdArrTerminationDate_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TrdArrDuration" xlink:label="TrdArrDuration" xlink:title="TrdArrDuration" />
    <link:label xlink:type="resource" xlink:label="ecd_TrdArrDuration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_TrdArrDuration" xml:lang="en-US" id="ecd_TrdArrDuration">Arrangement Duration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TrdArrDuration" xlink:to="ecd_TrdArrDuration" xlink:title="label: TrdArrDuration to ecd_TrdArrDuration" />
    <link:label xlink:type="resource" xlink:label="ecd_TrdArrDuration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_TrdArrDuration_lbl1" xml:lang="en-US" id="ecd_TrdArrDuration_lbl1">Trading Arrangement Duration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TrdArrDuration" xlink:to="ecd_TrdArrDuration_lbl1" xlink:title="label: TrdArrDuration to ecd_TrdArrDuration_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_TrdArrSecuritiesAggAvailAmt" xlink:label="TrdArrSecuritiesAggAvailAmt" xlink:title="TrdArrSecuritiesAggAvailAmt" />
    <link:label xlink:type="resource" xlink:label="ecd_TrdArrSecuritiesAggAvailAmt" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ecd_TrdArrSecuritiesAggAvailAmt" xml:lang="en-US" id="ecd_TrdArrSecuritiesAggAvailAmt">Aggregate Available</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TrdArrSecuritiesAggAvailAmt" xlink:to="ecd_TrdArrSecuritiesAggAvailAmt" xlink:title="label: TrdArrSecuritiesAggAvailAmt to ecd_TrdArrSecuritiesAggAvailAmt" />
    <link:label xlink:type="resource" xlink:label="ecd_TrdArrSecuritiesAggAvailAmt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ecd_TrdArrSecuritiesAggAvailAmt_lbl1" xml:lang="en-US" id="ecd_TrdArrSecuritiesAggAvailAmt_lbl1">Trading Arrangement, Securities Aggregate Available Amount</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:label="AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:title="AccretionAmortizationOfDiscountsAndPremiumsInvestments" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.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_StatementOfFinancialPositionAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfFinancialPositionAbstract" xml:lang="en-US" id="us-gaap_StatementOfFinancialPositionAbstract">CONSOLIDATED BALANCE SHEETS [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.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/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="CashAndCashEquivalentsAtCarryingValue" xlink:title="CashAndCashEquivalentsAtCarryingValue" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestPaidNet" xlink:label="InterestPaidNet" xlink:title="InterestPaidNet" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesIssued" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockSharesIssued" xml:lang="en-US" id="us-gaap_CommonStockSharesIssued">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" xlink:title="label: CommonStockSharesIssued to us-gaap_CommonStockSharesIssued" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesOutstanding" xlink:label="CommonStockSharesOutstanding" xlink:title="CommonStockSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesOutstanding" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockSharesOutstanding" xml:lang="en-US" id="us-gaap_CommonStockSharesOutstanding">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" xlink:title="label: CommonStockSharesOutstanding to us-gaap_CommonStockSharesOutstanding" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockValue" xlink:label="CommonStockValue" xlink:title="CommonStockValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockValue" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_CommonStockValue" xml:lang="en-US" id="us-gaap_CommonStockValue">Common stock, $0.001 par value; 300,000,000 shares authorized, 146,025,246 and 144,340,526 shares issued and outstanding at June 30, 2024 (unaudited) and December 31, 2023, 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" xlink:title="label: CommonStockValue to us-gaap_CommonStockValue" />
    <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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="ComprehensiveIncomeNetOfTax" xlink:title="ComprehensiveIncomeNetOfTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_ComprehensiveIncomeNetOfTax" xml:lang="en-US" id="us-gaap_ComprehensiveIncomeNetOfTax">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" xlink:title="label: ComprehensiveIncomeNetOfTax to us-gaap_ComprehensiveIncomeNetOfTax" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="ConcentrationRiskByTypeAxis" xlink:title="ConcentrationRiskByTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskByTypeAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskByTypeAxis" xml:lang="en-US" id="us-gaap_ConcentrationRiskByTypeAxis">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" xlink:title="label: ConcentrationRiskByTypeAxis to us-gaap_ConcentrationRiskByTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain" xlink:title="ConcentrationRiskTypeDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskTypeDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskTypeDomain" xml:lang="en-US" id="us-gaap_ConcentrationRiskTypeDomain">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" xlink:title="label: ConcentrationRiskTypeDomain to us-gaap_ConcentrationRiskTypeDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConvertibleDebtCurrent" xlink:label="ConvertibleDebtCurrent" xlink:title="ConvertibleDebtCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebtCurrent" xml:lang="en-US" id="us-gaap_ConvertibleDebtCurrent">0.125 percent convertible senior notes, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtCurrent" xlink:to="us-gaap_ConvertibleDebtCurrent" xlink:title="label: ConvertibleDebtCurrent to us-gaap_ConvertibleDebtCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtCurrent_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtCurrent_lbl1">Convertible Debt, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtCurrent" xlink:to="us-gaap_ConvertibleDebtCurrent_lbl1" xlink:title="label: ConvertibleDebtCurrent to us-gaap_ConvertibleDebtCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="CorporateDebtSecuritiesMember" xlink:title="CorporateDebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CorporateDebtSecuritiesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CorporateDebtSecuritiesMember" xml:lang="en-US" id="us-gaap_CorporateDebtSecuritiesMember">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" xlink:title="label: CorporateDebtSecuritiesMember to us-gaap_CorporateDebtSecuritiesMember" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="CostOfGoodsAndServicesSold" xlink:title="CostOfGoodsAndServicesSold" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSold" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfGoodsAndServicesSold" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSold">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" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesCurrent" xlink:label="LiabilitiesCurrent" xlink:title="LiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrent" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LiabilitiesCurrent" xml:lang="en-US" id="us-gaap_LiabilitiesCurrent">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" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesCurrentAbstract" xlink:label="LiabilitiesCurrentAbstract" xlink:title="LiabilitiesCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrentAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LiabilitiesCurrentAbstract" xml:lang="en-US" id="us-gaap_LiabilitiesCurrentAbstract">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" xlink:title="label: LiabilitiesCurrentAbstract to us-gaap_LiabilitiesCurrentAbstract" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_CustomerConcentrationRiskMember" xlink:label="CustomerConcentrationRiskMember" xlink:title="CustomerConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CustomerConcentrationRiskMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CustomerConcentrationRiskMember" xml:lang="en-US" id="us-gaap_CustomerConcentrationRiskMember">Strategic Partner [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CustomerConcentrationRiskMember" xlink:to="us-gaap_CustomerConcentrationRiskMember" xlink:title="label: CustomerConcentrationRiskMember to us-gaap_CustomerConcentrationRiskMember" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CustomerConcentrationRiskMember" xlink:to="us-gaap_CustomerConcentrationRiskMember_lbl1" xlink:title="label: CustomerConcentrationRiskMember to us-gaap_CustomerConcentrationRiskMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtDisclosureTextBlock" xlink:label="DebtDisclosureTextBlock" xlink:title="DebtDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtDisclosureTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtDisclosureTextBlock" xml:lang="en-US" id="us-gaap_DebtDisclosureTextBlock">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" xlink:title="label: DebtDisclosureTextBlock to us-gaap_DebtDisclosureTextBlock" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:label="DebtInstrumentCarryingAmount" xlink:title="DebtInstrumentCarryingAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentCarryingAmount" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentCarryingAmount" xml:lang="en-US" id="us-gaap_DebtInstrumentCarryingAmount">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" xlink:title="label: DebtInstrumentCarryingAmount to us-gaap_DebtInstrumentCarryingAmount" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="DebtInstrumentFaceAmount" xlink:title="DebtInstrumentFaceAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentFaceAmount" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_DebtInstrumentFaceAmount" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount">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" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:label="DebtInstrumentInterestRateEffectivePercentage" xlink:title="DebtInstrumentInterestRateEffectivePercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtInstrumentInterestRateEffectivePercentage" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateEffectivePercentage">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" xlink:title="label: DebtInstrumentInterestRateEffectivePercentage to us-gaap_DebtInstrumentInterestRateEffectivePercentage" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtInstrumentInterestRateStatedPercentage" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateStatedPercentage">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" xlink:title="label: DebtInstrumentInterestRateStatedPercentage to us-gaap_DebtInstrumentInterestRateStatedPercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentInterestRateStatedPercentage1" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateStatedPercentage1">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_DebtInstrumentInterestRateStatedPercentage1" xlink:title="label: DebtInstrumentInterestRateStatedPercentage to us-gaap_DebtInstrumentInterestRateStatedPercentage1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentMaturityDate" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentMaturityDate" xml:lang="en-US" id="us-gaap_DebtInstrumentMaturityDate">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" xlink:title="label: DebtInstrumentMaturityDate to us-gaap_DebtInstrumentMaturityDate" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentNameDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentNameDomain" xml:lang="en-US" id="us-gaap_DebtInstrumentNameDomain">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" xlink:title="label: DebtInstrumentNameDomain to us-gaap_DebtInstrumentNameDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentAxis" xml:lang="en-US" id="us-gaap_DebtInstrumentAxis">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" xlink:title="label: DebtInstrumentAxis to us-gaap_DebtInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="DebtInstrumentLineItems" xlink:title="DebtInstrumentLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentLineItems" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentLineItems" xml:lang="en-US" id="us-gaap_DebtInstrumentLineItems">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" xlink:title="label: DebtInstrumentLineItems to us-gaap_DebtInstrumentLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentTable" xlink:label="DebtInstrumentTable" xlink:title="DebtInstrumentTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentTable" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentTable" xml:lang="en-US" id="us-gaap_DebtInstrumentTable">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" xlink:title="label: DebtInstrumentTable to us-gaap_DebtInstrumentTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsOfDebtIssuanceCosts" xlink:label="PaymentsOfDebtIssuanceCosts" xlink:title="PaymentsOfDebtIssuanceCosts" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsOfDebtIssuanceCosts" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_PaymentsOfDebtIssuanceCosts" xml:lang="en-US" id="us-gaap_PaymentsOfDebtIssuanceCosts">1.75 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" xlink:title="label: PaymentsOfDebtIssuanceCosts to us-gaap_PaymentsOfDebtIssuanceCosts" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesMember" xlink:label="DebtSecuritiesMember" xlink:title="DebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtSecuritiesMember" xml:lang="en-US" id="us-gaap_DebtSecuritiesMember">Available-for-sale 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" xlink:title="label: DebtSecuritiesMember to us-gaap_DebtSecuritiesMember" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_EarningsPerShareDiluted" xlink:label="EarningsPerShareDiluted" xlink:title="EarningsPerShareDiluted" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EarningsPerShareDiluted" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EarningsPerShareDiluted" xml:lang="en-US" id="us-gaap_EarningsPerShareDiluted">Diluted net loss 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="EarningsPerShareDiluted" xlink:to="us-gaap_EarningsPerShareDiluted" xlink:title="label: EarningsPerShareDiluted to us-gaap_EarningsPerShareDiluted" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConsolidationPolicyTextBlock" xlink:label="ConsolidationPolicyTextBlock" xlink:title="ConsolidationPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConsolidationPolicyTextBlock" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConsolidationPolicyTextBlock" xml:lang="en-US" id="us-gaap_ConsolidationPolicyTextBlock">Consolidation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationPolicyTextBlock" xlink:to="us-gaap_ConsolidationPolicyTextBlock" xlink:title="label: ConsolidationPolicyTextBlock to us-gaap_ConsolidationPolicyTextBlock" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="AllocatedShareBasedCompensationExpense" xlink:title="AllocatedShareBasedCompensationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AllocatedShareBasedCompensationExpense" xml:lang="en-US" id="us-gaap_AllocatedShareBasedCompensationExpense">Stock-based compensation expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AllocatedShareBasedCompensationExpense" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense" xlink:title="label: AllocatedShareBasedCompensationExpense to us-gaap_AllocatedShareBasedCompensationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xml:lang="en-US" id="us-gaap_AllocatedShareBasedCompensationExpense_lbl1">Share-Based Payment Arrangement, Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AllocatedShareBasedCompensationExpense" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xlink:title="label: AllocatedShareBasedCompensationExpense to us-gaap_AllocatedShareBasedCompensationExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:title="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems">Share-based Compensation Arrangement by Share-based Payment Award, Compensation Cost [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:title="label: EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems to us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockMember" xlink:label="EmployeeStockMember" xlink:title="EmployeeStockMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeStockMember" xml:lang="en-US" id="us-gaap_EmployeeStockMember">ESPP [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockMember" xlink:to="us-gaap_EmployeeStockMember" xlink:title="label: EmployeeStockMember to us-gaap_EmployeeStockMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeStockMember_lbl1" xml:lang="en-US" id="us-gaap_EmployeeStockMember_lbl1">Employee Stock [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockMember" xlink:to="us-gaap_EmployeeStockMember_lbl1" xlink:title="label: EmployeeStockMember to us-gaap_EmployeeStockMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensation" xlink:label="ShareBasedCompensation" xlink:title="ShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensation" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensation" xml:lang="en-US" id="us-gaap_ShareBasedCompensation">Stock-based compensation expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensation" xlink:to="us-gaap_ShareBasedCompensation" xlink:title="label: ShareBasedCompensation to us-gaap_ShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensation_lbl1">Share-Based Payment Arrangement, Noncash Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensation" xlink:to="us-gaap_ShareBasedCompensation_lbl1" xlink:title="label: ShareBasedCompensation to us-gaap_ShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationAbstract" xlink:label="ShareBasedCompensationAbstract" xlink:title="ShareBasedCompensationAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationAbstract" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAbstract">Stock-based Compensation Expense [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAbstract" xlink:to="us-gaap_ShareBasedCompensationAbstract" xlink:title="label: ShareBasedCompensationAbstract to us-gaap_ShareBasedCompensationAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationAbstract_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAbstract_lbl1">Share-Based Payment Arrangement, Noncash Expense [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAbstract" xlink:to="us-gaap_ShareBasedCompensationAbstract_lbl1" xlink:title="label: ShareBasedCompensationAbstract to us-gaap_ShareBasedCompensationAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquitySecuritiesMember" xlink:label="EquitySecuritiesMember" xlink:title="EquitySecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesMember" xml:lang="en-US" id="us-gaap_EquitySecuritiesMember">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" xlink:title="label: EquitySecuritiesMember to us-gaap_EquitySecuritiesMember" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_GainLossOnInvestments" xlink:label="GainLossOnInvestments" xlink:title="GainLossOnInvestments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainLossOnInvestments" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_GainLossOnInvestments" xml:lang="en-US" id="us-gaap_GainLossOnInvestments">Gain (loss) on investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnInvestments" xlink:to="us-gaap_GainLossOnInvestments" xlink:title="label: GainLossOnInvestments to us-gaap_GainLossOnInvestments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainLossOnInvestments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GainLossOnInvestments_lbl1" xml:lang="en-US" id="us-gaap_GainLossOnInvestments_lbl1">Gain (Loss) on Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnInvestments" xlink:to="us-gaap_GainLossOnInvestments_lbl1" xlink:title="label: GainLossOnInvestments to us-gaap_GainLossOnInvestments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt" xlink:label="GainsLossesOnExtinguishmentOfDebt" xlink:title="GainsLossesOnExtinguishmentOfDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainsLossesOnExtinguishmentOfDebt" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_GainsLossesOnExtinguishmentOfDebt" xml:lang="en-US" id="us-gaap_GainsLossesOnExtinguishmentOfDebt">Gain on early retirement of debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainsLossesOnExtinguishmentOfDebt" xlink:to="us-gaap_GainsLossesOnExtinguishmentOfDebt" xlink:title="label: GainsLossesOnExtinguishmentOfDebt to us-gaap_GainsLossesOnExtinguishmentOfDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl1" xml:lang="en-US" id="us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl1">Gain (Loss) on Extinguishment of Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainsLossesOnExtinguishmentOfDebt" xlink:to="us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl1" xlink:title="label: GainsLossesOnExtinguishmentOfDebt to us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementAbstract" xlink:label="IncomeStatementAbstract" xlink:title="IncomeStatementAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeStatementAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeStatementAbstract" xml:lang="en-US" id="us-gaap_IncomeStatementAbstract">CONSOLIDATED STATEMENTS OF OPERATIONS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeStatementAbstract" xlink:to="us-gaap_IncomeStatementAbstract" xlink:title="label: IncomeStatementAbstract to us-gaap_IncomeStatementAbstract" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxDisclosureTextBlock" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_IncomeTaxDisclosureTextBlock" xml:lang="en-US" id="us-gaap_IncomeTaxDisclosureTextBlock">Income Taxes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxDisclosureTextBlock" xlink:to="us-gaap_IncomeTaxDisclosureTextBlock" xlink:title="label: IncomeTaxDisclosureTextBlock to us-gaap_IncomeTaxDisclosureTextBlock" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:label="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:title="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities">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" xlink:title="label: IncreaseDecreaseInOtherEmployeeRelatedLiabilities to us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:label="IncreaseDecreaseInOtherOperatingAssets" xlink:title="IncreaseDecreaseInOtherOperatingAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_IncreaseDecreaseInOtherOperatingAssets" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherOperatingAssets">Other current and long-term assets</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/2024/elts/us-gaap-2024.xsd#us-gaap_InterestExpense" xlink:label="InterestExpense" xlink:title="InterestExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestExpense" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_InterestExpense" xml:lang="en-US" id="us-gaap_InterestExpense">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" xlink:title="label: InterestExpense to us-gaap_InterestExpense" />
    <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, Operating and Nonoperating</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/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryFinishedGoods" xlink:label="InventoryFinishedGoods" xlink:title="InventoryFinishedGoods" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryFinishedGoods" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryFinishedGoods" xml:lang="en-US" id="us-gaap_InventoryFinishedGoods">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" xlink:title="label: InventoryFinishedGoods to us-gaap_InventoryFinishedGoods" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryNet" xlink:label="InventoryNet" xlink:title="InventoryNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryNet" xml:lang="en-US" id="us-gaap_InventoryNet">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" xlink:title="label: InventoryNet to us-gaap_InventoryNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_InventoryNet1" xml:lang="en-US" id="us-gaap_InventoryNet1">Total 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_InventoryNet1" xlink:title="label: InventoryNet to us-gaap_InventoryNet1" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryNetAbstract" xlink:label="InventoryNetAbstract" xlink:title="InventoryNetAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNetAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryNetAbstract" xml:lang="en-US" id="us-gaap_InventoryNetAbstract">Inventory [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" xlink:title="label: InventoryNetAbstract to us-gaap_InventoryNetAbstract" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryRawMaterials" xlink:label="InventoryRawMaterials" xlink:title="InventoryRawMaterials" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryRawMaterials" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryRawMaterials" xml:lang="en-US" id="us-gaap_InventoryRawMaterials">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" xlink:title="label: InventoryRawMaterials to us-gaap_InventoryRawMaterials" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryWorkInProcess" xlink:label="InventoryWorkInProcess" xlink:title="InventoryWorkInProcess" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWorkInProcess" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryWorkInProcess" xml:lang="en-US" id="us-gaap_InventoryWorkInProcess">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" xlink:title="label: InventoryWorkInProcess to us-gaap_InventoryWorkInProcess" />
    <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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InvestmentIncomeNet" xlink:label="InvestmentIncomeNet" xlink:title="InvestmentIncomeNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentIncomeNet" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet">Investment income</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" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentIncomeNet_lbl1" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet_lbl1">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_lbl1" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsAbstract" xml:lang="en-US" id="us-gaap_InvestmentsAbstract">Investments [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_Liabilities" xml:lang="en-US" id="us-gaap_Liabilities">Total liabilities</link:label>
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    <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/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="LiabilitiesAndStockholdersEquity" xlink:title="LiabilitiesAndStockholdersEquity" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LiabilitiesAndStockholdersEquity" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquity">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" xlink:title="label: LiabilitiesAndStockholdersEquity to us-gaap_LiabilitiesAndStockholdersEquity" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquityAbstract">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" xlink:title="label: LiabilitiesAndStockholdersEquityAbstract to us-gaap_LiabilitiesAndStockholdersEquityAbstract" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="NetCashProvidedByUsedInFinancingActivities" xlink:title="NetCashProvidedByUsedInFinancingActivities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivities" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivities">Net cash provided by financing activities</link:label>
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    <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>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:title="label: NetCashProvidedByUsedInInvestingActivities to us-gaap_NetCashProvidedByUsedInInvestingActivities" />
    <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_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract">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" xlink:title="label: NetCashProvidedByUsedInInvestingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" />
    <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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="NetCashProvidedByUsedInOperatingActivities" xlink:title="NetCashProvidedByUsedInOperatingActivities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivities" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivities">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" xlink:title="label: NetCashProvidedByUsedInOperatingActivities to us-gaap_NetCashProvidedByUsedInOperatingActivities" />
    <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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInOperatingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract">Operating activities:</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" xlink:title="label: NetCashProvidedByUsedInOperatingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetIncomeLoss" xml:lang="en-US" id="us-gaap_NetIncomeLoss">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" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetIncomeLoss1" xml:lang="en-US" id="us-gaap_NetIncomeLoss1">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_NetIncomeLoss1" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss1" />
    <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)</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/2024/elts/us-gaap-2024.xsd#us-gaap_NonoperatingIncomeExpenseAbstract" xlink:label="NonoperatingIncomeExpenseAbstract" xlink:title="NonoperatingIncomeExpenseAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NonoperatingIncomeExpenseAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NonoperatingIncomeExpenseAbstract" xml:lang="en-US" id="us-gaap_NonoperatingIncomeExpenseAbstract">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" xlink:title="label: NonoperatingIncomeExpenseAbstract to us-gaap_NonoperatingIncomeExpenseAbstract" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingIncomeLoss" xlink:label="OperatingIncomeLoss" xlink:title="OperatingIncomeLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingIncomeLoss" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_OperatingIncomeLoss" xml:lang="en-US" id="us-gaap_OperatingIncomeLoss">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" xlink:title="label: OperatingIncomeLoss to us-gaap_OperatingIncomeLoss" />
    <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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:label="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:title="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xml:lang="en-US" id="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock">Organization and Basis of Presentation</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:to="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl1" xlink:title="label: OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock to us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherAssetsCurrent" xlink:label="OtherAssetsCurrent" xlink:title="OtherAssetsCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAssetsCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherAssetsCurrent" xml:lang="en-US" id="us-gaap_OtherAssetsCurrent">Other current assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAssetsCurrent" xlink:to="us-gaap_OtherAssetsCurrent" xlink:title="label: OtherAssetsCurrent to us-gaap_OtherAssetsCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAssetsCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherAssetsCurrent_lbl1" xml:lang="en-US" id="us-gaap_OtherAssetsCurrent_lbl1">Other Assets, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAssetsCurrent" xlink:to="us-gaap_OtherAssetsCurrent_lbl1" xlink:title="label: OtherAssetsCurrent to us-gaap_OtherAssetsCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="OtherNonoperatingIncomeExpense" xlink:title="OtherNonoperatingIncomeExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNonoperatingIncomeExpense" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherNonoperatingIncomeExpense" xml:lang="en-US" id="us-gaap_OtherNonoperatingIncomeExpense">Other income</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherNonoperatingIncomeExpense" xlink:to="us-gaap_OtherNonoperatingIncomeExpense" xlink:title="label: OtherNonoperatingIncomeExpense to us-gaap_OtherNonoperatingIncomeExpense" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:label="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xml:lang="en-US" id="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities">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" xlink:title="label: ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities to us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromConvertibleDebt" xlink:label="ProceedsFromConvertibleDebt" xlink:title="ProceedsFromConvertibleDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromConvertibleDebt" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromConvertibleDebt" xml:lang="en-US" id="us-gaap_ProceedsFromConvertibleDebt">Proceeds from issuance of 1.75 percent convertible senior 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" xlink:title="label: ProceedsFromConvertibleDebt to us-gaap_ProceedsFromConvertibleDebt" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfWarrants" xlink:label="ProceedsFromIssuanceOfWarrants" xlink:title="ProceedsFromIssuanceOfWarrants" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfWarrants" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromIssuanceOfWarrants" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfWarrants">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" xlink:title="label: ProceedsFromIssuanceOfWarrants to us-gaap_ProceedsFromIssuanceOfWarrants" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="PropertyPlantAndEquipmentNet" xlink:title="PropertyPlantAndEquipmentNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentNet" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentNet" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentNet">Property, plant and equipment, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentNet" xlink:to="us-gaap_PropertyPlantAndEquipmentNet" xlink:title="label: PropertyPlantAndEquipmentNet to us-gaap_PropertyPlantAndEquipmentNet" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_SellingGeneralAndAdministrativeExpense" xlink:label="SellingGeneralAndAdministrativeExpense" xlink:title="SellingGeneralAndAdministrativeExpense" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems">Share-based Compensation Arrangement by Share-based Payment Award [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShortTermInvestments" xlink:label="ShortTermInvestments" xlink:title="ShortTermInvestments" />
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    <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" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_SignificantAccountingPoliciesTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SignificantAccountingPoliciesTextBlock" xml:lang="en-US" id="us-gaap_SignificantAccountingPoliciesTextBlock">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" xlink:title="label: SignificantAccountingPoliciesTextBlock to us-gaap_SignificantAccountingPoliciesTextBlock" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_StatementOfCashFlowsAbstract" xlink:label="StatementOfCashFlowsAbstract" xlink:title="StatementOfCashFlowsAbstract" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfCashFlowsAbstract" xlink:to="us-gaap_StatementOfCashFlowsAbstract" xlink:title="label: StatementOfCashFlowsAbstract to us-gaap_StatementOfCashFlowsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:label="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:title="StatementOfIncomeAndComprehensiveIncomeAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xml:lang="en-US" id="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract">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" xlink:title="label: StatementOfIncomeAndComprehensiveIncomeAbstract to us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementOfStockholdersEquityAbstract" xlink:label="StatementOfStockholdersEquityAbstract" xlink:title="StatementOfStockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfStockholdersEquityAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfStockholdersEquityAbstract" xml:lang="en-US" id="us-gaap_StatementOfStockholdersEquityAbstract">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" xlink:title="label: StatementOfStockholdersEquityAbstract to us-gaap_StatementOfStockholdersEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquityAbstract" xlink:label="StockholdersEquityAbstract" xlink:title="StockholdersEquityAbstract" />
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    <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" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventTypeAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventTypeAxis" xml:lang="en-US" id="us-gaap_SubsequentEventTypeAxis">Subsequent Event Type [Axis]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="SubsequentEventTypeDomain" xlink:title="SubsequentEventTypeDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventTypeDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventTypeDomain" xml:lang="en-US" id="us-gaap_SubsequentEventTypeDomain">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" xlink:title="label: SubsequentEventTypeDomain to us-gaap_SubsequentEventTypeDomain" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_SupplementalCashFlowInformationAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SupplementalCashFlowInformationAbstract" xml:lang="en-US" id="us-gaap_SupplementalCashFlowInformationAbstract">Supplemental disclosures of cash flow information:</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsCurrentAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AssetsCurrentAbstract" xml:lang="en-US" id="us-gaap_AssetsCurrentAbstract">Current assets:</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel1Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueInputsLevel1Member" xml:lang="en-US" id="us-gaap_FairValueInputsLevel1Member">Quoted Prices in Active Markets (Level 1) [Member]</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:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel2Member" xlink:label="FairValueInputsLevel2Member" xlink:title="FairValueInputsLevel2Member" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel2Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueInputsLevel2Member" xml:lang="en-US" id="us-gaap_FairValueInputsLevel2Member">Significant Other Observable Inputs (Level 2) [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_StockholdersEquity1" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_StockholdersEquity1" xml:lang="en-US" id="us-gaap_StockholdersEquity1">Balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquity" xlink:to="us-gaap_StockholdersEquity1" xlink:title="label: StockholdersEquity to us-gaap_StockholdersEquity1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquityComponentDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquityComponentDomain" xml:lang="en-US" id="us-gaap_EquityComponentDomain">Equity Component [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityComponentDomain" xlink:to="us-gaap_EquityComponentDomain" xlink:title="label: EquityComponentDomain to us-gaap_EquityComponentDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="EmployeeStockOptionMember" xlink:title="EmployeeStockOptionMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockOptionMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeStockOptionMember" xml:lang="en-US" id="us-gaap_EmployeeStockOptionMember">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" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember" />
    <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">Employee Stock 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/2024/elts/us-gaap-2024.xsd#us-gaap_RealizedInvestmentGainsLosses" xlink:label="RealizedInvestmentGainsLosses" xlink:title="RealizedInvestmentGainsLosses" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RealizedInvestmentGainsLosses" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_RealizedInvestmentGainsLosses" xml:lang="en-US" id="us-gaap_RealizedInvestmentGainsLosses">Loss (gain) on investments</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_RealizedInvestmentGainsLosses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RealizedInvestmentGainsLosses_lbl1" xml:lang="en-US" id="us-gaap_RealizedInvestmentGainsLosses_lbl1">Realized Investment Gains (Losses)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RealizedInvestmentGainsLosses" xlink:to="us-gaap_RealizedInvestmentGainsLosses_lbl1" xlink:title="label: RealizedInvestmentGainsLosses to us-gaap_RealizedInvestmentGainsLosses_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:label="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:title="StockIssuedDuringPeriodSharesShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation">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" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensation to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_OtherLiabilitiesDisclosureTextBlock" xlink:label="OtherLiabilitiesDisclosureTextBlock" xlink:title="OtherLiabilitiesDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherLiabilitiesDisclosureTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherLiabilitiesDisclosureTextBlock" xml:lang="en-US" id="us-gaap_OtherLiabilitiesDisclosureTextBlock">Liability Related to Sale of Future Royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherLiabilitiesDisclosureTextBlock" xlink:to="us-gaap_OtherLiabilitiesDisclosureTextBlock" xlink:title="label: OtherLiabilitiesDisclosureTextBlock to us-gaap_OtherLiabilitiesDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherLiabilitiesDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherLiabilitiesDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_OtherLiabilitiesDisclosureTextBlock_lbl1">Other Liabilities Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherLiabilitiesDisclosureTextBlock" xlink:to="us-gaap_OtherLiabilitiesDisclosureTextBlock_lbl1" xlink:title="label: OtherLiabilitiesDisclosureTextBlock to us-gaap_OtherLiabilitiesDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CollaborativeArrangementDisclosureTextBlock" xlink:label="CollaborativeArrangementDisclosureTextBlock" xlink:title="CollaborativeArrangementDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CollaborativeArrangementDisclosureTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CollaborativeArrangementDisclosureTextBlock" xml:lang="en-US" id="us-gaap_CollaborativeArrangementDisclosureTextBlock">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" xlink:title="label: CollaborativeArrangementDisclosureTextBlock to us-gaap_CollaborativeArrangementDisclosureTextBlock" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="CostsAndExpensesAbstract" xlink:title="CostsAndExpensesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostsAndExpensesAbstract" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract">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" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract" />
    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostsAndExpenses" xlink:label="CostsAndExpenses" xlink:title="CostsAndExpenses" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_CostsAndExpenses" xml:lang="en-US" id="us-gaap_CostsAndExpenses">Total operating expenses</link:label>
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    <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/2024/elts/us-gaap-2024.xsd#us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:label="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:title="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xml:lang="en-US" id="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract">Supplemental disclosures of non-cash investing and financing activities:</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract">Weighted-Average Assumptions [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharesIssued" xlink:label="SharesIssued" xlink:title="SharesIssued" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued" xlink:title="label: SharesIssued to us-gaap_SharesIssued" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EarningsPerShareTextBlock" xlink:label="EarningsPerShareTextBlock" xlink:title="EarningsPerShareTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EarningsPerShareTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EarningsPerShareTextBlock" xml:lang="en-US" id="us-gaap_EarningsPerShareTextBlock">Basic and Diluted Net Loss Per Share</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_EarningsPerShareTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EarningsPerShareTextBlock_lbl1" xml:lang="en-US" id="us-gaap_EarningsPerShareTextBlock_lbl1">Earnings Per Share [Text Block]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccruedIncomeTaxesCurrent" xlink:label="AccruedIncomeTaxesCurrent" xlink:title="AccruedIncomeTaxesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedIncomeTaxesCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AccruedIncomeTaxesCurrent" xml:lang="en-US" id="us-gaap_AccruedIncomeTaxesCurrent">Income taxes payable</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsPayableCurrent" xlink:label="AccountsPayableCurrent" xlink:title="AccountsPayableCurrent" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedLiabilitiesCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AccruedLiabilitiesCurrent" xml:lang="en-US" id="us-gaap_AccruedLiabilitiesCurrent">Accrued liabilities</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedLiabilitiesCurrent1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_AccruedLiabilitiesCurrent1" xml:lang="en-US" id="us-gaap_AccruedLiabilitiesCurrent1">Total accrued liabilities</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesCurrent" xlink:to="us-gaap_AccruedLiabilitiesCurrent_lbl2" xlink:title="label: AccruedLiabilitiesCurrent to us-gaap_AccruedLiabilitiesCurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="EmployeeRelatedLiabilitiesCurrent" xlink:title="EmployeeRelatedLiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeRelatedLiabilitiesCurrent" xml:lang="en-US" id="us-gaap_EmployeeRelatedLiabilitiesCurrent">Accrued compensation</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1">Employee-related Liabilities, Current</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_lbl1" xlink:title="label: EmployeeRelatedLiabilitiesCurrent to us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherAccruedLiabilitiesCurrent" xlink:label="OtherAccruedLiabilitiesCurrent" xlink:title="OtherAccruedLiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAccruedLiabilitiesCurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherAccruedLiabilitiesCurrent" xml:lang="en-US" id="us-gaap_OtherAccruedLiabilitiesCurrent">Other miscellaneous expenses</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAccruedLiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherAccruedLiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_OtherAccruedLiabilitiesCurrent_lbl1">Other Accrued Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAccruedLiabilitiesCurrent" xlink:to="us-gaap_OtherAccruedLiabilitiesCurrent_lbl1" xlink:title="label: OtherAccruedLiabilitiesCurrent to us-gaap_OtherAccruedLiabilitiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccruedLiabilitiesCurrentAbstract" xlink:label="AccruedLiabilitiesCurrentAbstract" xlink:title="AccruedLiabilitiesCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedLiabilitiesCurrentAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AccruedLiabilitiesCurrentAbstract" xml:lang="en-US" id="us-gaap_AccruedLiabilitiesCurrentAbstract">Accrued Liabilities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesCurrentAbstract" xlink:to="us-gaap_AccruedLiabilitiesCurrentAbstract" xlink:title="label: AccruedLiabilitiesCurrentAbstract to us-gaap_AccruedLiabilitiesCurrentAbstract" />
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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_lbl1" xlink:title="label: AccruedLiabilitiesCurrentAbstract to us-gaap_AccruedLiabilitiesCurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:label="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:title="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.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/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:label="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:title="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsForHedgeFinancingActivities" xlink:label="PaymentsForHedgeFinancingActivities" xlink:title="PaymentsForHedgeFinancingActivities" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:label="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:title="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueMeasurementsRecurringMember" xlink:to="us-gaap_FairValueMeasurementsRecurringMember_lbl1" xlink:title="label: FairValueMeasurementsRecurringMember to us-gaap_FairValueMeasurementsRecurringMember_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
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    <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" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xml:lang="en-US" id="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock">Contract Maturity of Available-for-Sale Securities</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_BasisOfAccountingPolicyPolicyTextBlock" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_BasisOfAccountingPolicyPolicyTextBlock" xml:lang="en-US" id="us-gaap_BasisOfAccountingPolicyPolicyTextBlock">Basis of Presentation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BasisOfAccountingPolicyPolicyTextBlock" xlink:to="us-gaap_BasisOfAccountingPolicyPolicyTextBlock" xlink:title="label: BasisOfAccountingPolicyPolicyTextBlock to us-gaap_BasisOfAccountingPolicyPolicyTextBlock" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions">Unrecognized compensation expense related to non-vested stock options</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl1" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl1" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FinancialInstrumentAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FinancialInstrumentAxis" xml:lang="en-US" id="us-gaap_FinancialInstrumentAxis">Financial Instrument [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FinancialInstrumentAxis" xlink:to="us-gaap_FinancialInstrumentAxis" xlink:title="label: FinancialInstrumentAxis to us-gaap_FinancialInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PerformanceSharesMember" xlink:label="PerformanceSharesMember" xlink:title="PerformanceSharesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PerformanceSharesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PerformanceSharesMember" xml:lang="en-US" id="us-gaap_PerformanceSharesMember">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" xlink:title="label: PerformanceSharesMember to us-gaap_PerformanceSharesMember" />
    <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/2024/elts/us-gaap-2024.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" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BalanceSheetLocationAxis" xlink:label="BalanceSheetLocationAxis" xlink:title="BalanceSheetLocationAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_BalanceSheetLocationAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_BalanceSheetLocationAxis" xml:lang="en-US" id="us-gaap_BalanceSheetLocationAxis">Balance Sheet Location [Axis]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventMember" xml:lang="en-US" id="us-gaap_SubsequentEventMember">Subsequent Event [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeStatementLocationDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeStatementLocationDomain" xml:lang="en-US" id="us-gaap_IncomeStatementLocationDomain">Income Statement Location [Domain]</link:label>
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    <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/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1">Vesting period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1 to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Award Vesting Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1 to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1">Weighted average period for recognition</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1 to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1">Share-Based Payment Arrangement, Nonvested Award, Cost Not yet Recognized, Period for Recognition</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1 to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NumberOfOperatingSegments" xlink:label="NumberOfOperatingSegments" xlink:title="NumberOfOperatingSegments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NumberOfOperatingSegments" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NumberOfOperatingSegments" xml:lang="en-US" id="us-gaap_NumberOfOperatingSegments">Number of operating segments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfOperatingSegments" xlink:to="us-gaap_NumberOfOperatingSegments" xlink:title="label: NumberOfOperatingSegments to us-gaap_NumberOfOperatingSegments" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherCurrentAssetsMember" xlink:label="OtherCurrentAssetsMember" xlink:title="OtherCurrentAssetsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherCurrentAssetsMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherCurrentAssetsMember" xml:lang="en-US" id="us-gaap_OtherCurrentAssetsMember">Other Current Assets [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCurrentAssetsMember" xlink:to="us-gaap_OtherCurrentAssetsMember" xlink:title="label: OtherCurrentAssetsMember to us-gaap_OtherCurrentAssetsMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:label="SellingGeneralAndAdministrativeExpensesMember" xlink:title="SellingGeneralAndAdministrativeExpensesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpensesMember" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpensesMember">Selling, General and Administrative Expense [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SellingGeneralAndAdministrativeExpensesMember" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:title="label: SellingGeneralAndAdministrativeExpensesMember to us-gaap_SellingGeneralAndAdministrativeExpensesMember" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SellingGeneralAndAdministrativeExpensesMember" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xlink:title="label: SellingGeneralAndAdministrativeExpensesMember to us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskPercentage1" xlink:label="ConcentrationRiskPercentage1" xlink:title="ConcentrationRiskPercentage1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskPercentage1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskPercentage1" xml:lang="en-US" id="us-gaap_ConcentrationRiskPercentage1">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" xlink:title="label: ConcentrationRiskPercentage1 to us-gaap_ConcentrationRiskPercentage1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1" xlink:label="DebtInstrumentConvertibleConversionPrice1" xlink:title="DebtInstrumentConvertibleConversionPrice1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentConvertibleConversionPrice1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentConvertibleConversionPrice1" xml:lang="en-US" id="us-gaap_DebtInstrumentConvertibleConversionPrice1">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" xlink:title="label: DebtInstrumentConvertibleConversionPrice1 to us-gaap_DebtInstrumentConvertibleConversionPrice1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="BalanceSheetLocationDomain" xlink:title="BalanceSheetLocationDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_BalanceSheetLocationDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_BalanceSheetLocationDomain" xml:lang="en-US" id="us-gaap_BalanceSheetLocationDomain">Balance Sheet Location [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BalanceSheetLocationDomain" xlink:to="us-gaap_BalanceSheetLocationDomain" xlink:title="label: BalanceSheetLocationDomain to us-gaap_BalanceSheetLocationDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfSalesMember" xlink:label="CostOfSalesMember" xlink:title="CostOfSalesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfSalesMember" xml:lang="en-US" id="us-gaap_CostOfSalesMember">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" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_InvestmentTextBlock" xlink:label="InvestmentTextBlock" xlink:title="InvestmentTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentTextBlock" xml:lang="en-US" id="us-gaap_InvestmentTextBlock">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" xlink:title="label: InvestmentTextBlock to us-gaap_InvestmentTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InvestmentTextBlock_lbl1">Investment [Text Block]</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_lbl1" xlink:title="label: InvestmentTextBlock to us-gaap_InvestmentTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueNetAssetLiabilityAbstract" xlink:label="FairValueNetAssetLiabilityAbstract" xlink:title="FairValueNetAssetLiabilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueNetAssetLiabilityAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueNetAssetLiabilityAbstract" xml:lang="en-US" id="us-gaap_FairValueNetAssetLiabilityAbstract">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" xlink:title="label: FairValueNetAssetLiabilityAbstract to us-gaap_FairValueNetAssetLiabilityAbstract" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_ConvertibleDebtTableTextBlock" xlink:label="ConvertibleDebtTableTextBlock" xlink:title="ConvertibleDebtTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtTableTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebtTableTextBlock" xml:lang="en-US" id="us-gaap_ConvertibleDebtTableTextBlock">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" xlink:title="label: ConvertibleDebtTableTextBlock to us-gaap_ConvertibleDebtTableTextBlock" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_OtherNoncurrentLiabilitiesTableTextBlock" xlink:label="OtherNoncurrentLiabilitiesTableTextBlock" xlink:title="OtherNoncurrentLiabilitiesTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock" xml:lang="en-US" id="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock">Liability Related to Sale of Future Royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherNoncurrentLiabilitiesTableTextBlock" xlink:to="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock" xlink:title="label: OtherNoncurrentLiabilitiesTableTextBlock to us-gaap_OtherNoncurrentLiabilitiesTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1">Other Noncurrent Liabilities [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherNoncurrentLiabilitiesTableTextBlock" xlink:to="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1" xlink:title="label: OtherNoncurrentLiabilitiesTableTextBlock to us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage">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" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_AwardDateAxis" xlink:label="AwardDateAxis" xlink:title="AwardDateAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AwardDateAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AwardDateAxis" xml:lang="en-US" id="us-gaap_AwardDateAxis">Award Date [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AwardDateAxis" xlink:to="us-gaap_AwardDateAxis" xlink:title="label: AwardDateAxis to us-gaap_AwardDateAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardDateDomain" xlink:label="AwardDateDomain" xlink:title="AwardDateDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AwardDateDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AwardDateDomain" xml:lang="en-US" id="us-gaap_AwardDateDomain">Award Date [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AwardDateDomain" xlink:to="us-gaap_AwardDateDomain" xlink:title="label: AwardDateDomain to us-gaap_AwardDateDomain" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryCurrentTable" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryCurrentTable" xml:lang="en-US" id="us-gaap_InventoryCurrentTable">Inventory, Current [Table]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryLineItems" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryLineItems" xml:lang="en-US" id="us-gaap_InventoryLineItems">Inventory [Line Items]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:role="http://www.xbrl.org/2009/role/negatedTotalLabel" xlink:title="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xml:lang="en-US" id="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax">Gross unrealized losses</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:title="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:title="label: AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax to us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl1" xlink:title="label: AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax to us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract">Unrealized Losses [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl1" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:label="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:title="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract">Available-for-sale Debt 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" xlink:title="label: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl1" xlink:title="label: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueTableTextBlock" xlink:label="DisaggregationOfRevenueTableTextBlock" xlink:title="DisaggregationOfRevenueTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisaggregationOfRevenueTableTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DisaggregationOfRevenueTableTextBlock" xml:lang="en-US" id="us-gaap_DisaggregationOfRevenueTableTextBlock">Revenues</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="DisaggregationOfRevenueTable" xlink:title="DisaggregationOfRevenueTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisaggregationOfRevenueTable" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DisaggregationOfRevenueTable" xml:lang="en-US" id="us-gaap_DisaggregationOfRevenueTable">Disaggregation of Revenue [Table]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="DisaggregationOfRevenueLineItems" xlink:title="DisaggregationOfRevenueLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisaggregationOfRevenueLineItems" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DisaggregationOfRevenueLineItems" xml:lang="en-US" id="us-gaap_DisaggregationOfRevenueLineItems">Disaggregation of Revenue [Line Items]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerAssetNetCurrent" xlink:label="ContractWithCustomerAssetNetCurrent" xlink:title="ContractWithCustomerAssetNetCurrent" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerAbstract" xlink:label="RevenueFromContractWithCustomerAbstract" xlink:title="RevenueFromContractWithCustomerAbstract" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerTextBlock" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerTextBlock">Revenues</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerAssetAndLiabilityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerAssetAndLiabilityAbstract_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerAssetAndLiabilityAbstract_lbl1">Contract with Customer, Contract Asset, Contract Liability, and Receivable [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiUnrealizedLoss" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_EquitySecuritiesFvNiUnrealizedLoss" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiUnrealizedLoss">Unrealized loss on equity securities</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" xlink:title="label: EquitySecuritiesFvNiUnrealizedLoss to us-gaap_EquitySecuritiesFvNiUnrealizedLoss" />
    <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/2024/elts/us-gaap-2024.xsd#us-gaap_GranteeStatusAxis" xlink:label="GranteeStatusAxis" xlink:title="GranteeStatusAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GranteeStatusAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GranteeStatusAxis" xml:lang="en-US" id="us-gaap_GranteeStatusAxis">Grantee Status [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GranteeStatusAxis" xlink:to="us-gaap_GranteeStatusAxis" xlink:title="label: GranteeStatusAxis to us-gaap_GranteeStatusAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GranteeStatusDomain" xlink:label="GranteeStatusDomain" xlink:title="GranteeStatusDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GranteeStatusDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GranteeStatusDomain" xml:lang="en-US" id="us-gaap_GranteeStatusDomain">Grantee Status [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GranteeStatusDomain" xlink:to="us-gaap_GranteeStatusDomain" xlink:title="label: GranteeStatusDomain to us-gaap_GranteeStatusDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedPaymentArrangementEmployeeMember" xlink:label="ShareBasedPaymentArrangementEmployeeMember" xlink:title="ShareBasedPaymentArrangementEmployeeMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedPaymentArrangementEmployeeMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedPaymentArrangementEmployeeMember" xml:lang="en-US" id="us-gaap_ShareBasedPaymentArrangementEmployeeMember">Employees [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementEmployeeMember" xlink:to="us-gaap_ShareBasedPaymentArrangementEmployeeMember" xlink:title="label: ShareBasedPaymentArrangementEmployeeMember to us-gaap_ShareBasedPaymentArrangementEmployeeMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1">Share-Based Payment Arrangement, Employee [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementEmployeeMember" xlink:to="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" xlink:title="label: ShareBasedPaymentArrangementEmployeeMember to us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:label="DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:title="DebtSecuritiesAvailableForSaleAmortizedCostCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent">Amortized cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:title="label: DebtSecuritiesAvailableForSaleAmortizedCostCurrent to us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1">Debt Securities, Available-for-Sale, Amortized Cost, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAmortizedCostCurrent to us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:label="DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:title="DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent">Amortized cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:title="label: DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent to us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1">Debt Securities, Available-for-Sale, Amortized Cost, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent to us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:label="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:title="OperatingLeaseRightOfUseAssetAmortizationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense">Amortization of right-of-use operating lease assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:to="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:title="label: OperatingLeaseRightOfUseAssetAmortizationExpense to us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1">Operating Lease, Right-of-Use Asset, Periodic Reduction</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:to="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" xlink:title="label: OperatingLeaseRightOfUseAssetAmortizationExpense to us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquitySecuritiesFVNIAbstract" xlink:label="EquitySecuritiesFVNIAbstract" xlink:title="EquitySecuritiesFVNIAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFVNIAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesFVNIAbstract" xml:lang="en-US" id="us-gaap_EquitySecuritiesFVNIAbstract">Equity Securities [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" xlink:title="label: EquitySecuritiesFVNIAbstract to us-gaap_EquitySecuritiesFVNIAbstract" />
    <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/srt/2024/elts/srt-2024.xsd#srt_ExecutiveOfficerMember" xlink:label="ExecutiveOfficerMember" xlink:title="ExecutiveOfficerMember" />
    <link:label xlink:type="resource" xlink:label="srt_ExecutiveOfficerMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ExecutiveOfficerMember" xml:lang="en-US" id="srt_ExecutiveOfficerMember">Executive Officers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ExecutiveOfficerMember" xlink:to="srt_ExecutiveOfficerMember" xlink:title="label: ExecutiveOfficerMember to srt_ExecutiveOfficerMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:label xlink:type="resource" xlink:label="srt_RangeAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RangeAxis" xml:lang="en-US" id="srt_RangeAxis">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" xlink:title="label: RangeAxis to srt_RangeAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:label xlink:type="resource" xlink:label="srt_RangeMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RangeMember" xml:lang="en-US" id="srt_RangeMember">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" xlink:title="label: RangeMember to srt_RangeMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MaximumMember" xlink:label="MaximumMember" xlink:title="MaximumMember" />
    <link:label xlink:type="resource" xlink:label="srt_MaximumMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MaximumMember" xml:lang="en-US" id="srt_MaximumMember">Maximum [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumMember" xlink:to="srt_MaximumMember" xlink:title="label: MaximumMember to srt_MaximumMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MinimumMember" xlink:label="MinimumMember" xlink:title="MinimumMember" />
    <link:label xlink:type="resource" xlink:label="srt_MinimumMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MinimumMember" xml:lang="en-US" id="srt_MinimumMember">Minimum [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinimumMember" xlink:to="srt_MinimumMember" xlink:title="label: MinimumMember to srt_MinimumMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ProductsAndServicesDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductsAndServicesDomain" xml:lang="en-US" id="srt_ProductsAndServicesDomain">Product and Service [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" xlink:title="label: ProductsAndServicesDomain to srt_ProductsAndServicesDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:label xlink:type="resource" xlink:label="srt_ProductOrServiceAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductOrServiceAxis" xml:lang="en-US" id="srt_ProductOrServiceAxis">Product and Service [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" xlink:title="label: ProductOrServiceAxis to srt_ProductOrServiceAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_CoverAbstract" xlink:label="CoverAbstract" xlink:title="CoverAbstract" />
    <link:label xlink:type="resource" xlink:label="dei_CoverAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CoverAbstract" xml:lang="en-US" id="dei_CoverAbstract">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" xlink:title="label: CoverAbstract to dei_CoverAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_DocumentType" xlink:label="DocumentType" xlink:title="DocumentType" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentType" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentType" xml:lang="en-US" id="dei_DocumentType">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" xlink:title="label: DocumentType to dei_DocumentType" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_DocumentQuarterlyReport" xlink:label="DocumentQuarterlyReport" xlink:title="DocumentQuarterlyReport" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentQuarterlyReport" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentQuarterlyReport" xml:lang="en-US" id="dei_DocumentQuarterlyReport">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" xlink:title="label: DocumentQuarterlyReport to dei_DocumentQuarterlyReport" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_DocumentTransitionReport" xlink:label="DocumentTransitionReport" xlink:title="DocumentTransitionReport" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentTransitionReport" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentTransitionReport" xml:lang="en-US" id="dei_DocumentTransitionReport">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" xlink:title="label: DocumentTransitionReport to dei_DocumentTransitionReport" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityInteractiveDataCurrent" xlink:label="EntityInteractiveDataCurrent" xlink:title="EntityInteractiveDataCurrent" />
    <link:label xlink:type="resource" xlink:label="dei_EntityInteractiveDataCurrent" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityInteractiveDataCurrent" xml:lang="en-US" id="dei_EntityInteractiveDataCurrent">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" xlink:title="label: EntityInteractiveDataCurrent to dei_EntityInteractiveDataCurrent" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_AmendmentFlag" xlink:label="AmendmentFlag" xlink:title="AmendmentFlag" />
    <link:label xlink:type="resource" xlink:label="dei_AmendmentFlag" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AmendmentFlag" xml:lang="en-US" id="dei_AmendmentFlag">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" xlink:title="label: AmendmentFlag to dei_AmendmentFlag" />
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    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalYearFocus" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalYearFocus" xml:lang="en-US" id="dei_DocumentFiscalYearFocus">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" xlink:title="label: DocumentFiscalYearFocus to dei_DocumentFiscalYearFocus" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_DocumentFiscalPeriodFocus" xlink:label="DocumentFiscalPeriodFocus" xlink:title="DocumentFiscalPeriodFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalPeriodFocus" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalPeriodFocus" xml:lang="en-US" id="dei_DocumentFiscalPeriodFocus">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" xlink:title="label: DocumentFiscalPeriodFocus to dei_DocumentFiscalPeriodFocus" />
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    <link:label xlink:type="resource" xlink:label="dei_DocumentPeriodEndDate" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentPeriodEndDate" xml:lang="en-US" id="dei_DocumentPeriodEndDate">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" xlink:title="label: DocumentPeriodEndDate to dei_DocumentPeriodEndDate" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityRegistrantName" xlink:label="EntityRegistrantName" xlink:title="EntityRegistrantName" />
    <link:label xlink:type="resource" xlink:label="dei_EntityRegistrantName" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityRegistrantName" xml:lang="en-US" id="dei_EntityRegistrantName">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" xlink:title="label: EntityRegistrantName to dei_EntityRegistrantName" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityCentralIndexKey" xlink:label="EntityCentralIndexKey" xlink:title="EntityCentralIndexKey" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCentralIndexKey" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCentralIndexKey" xml:lang="en-US" id="dei_EntityCentralIndexKey">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" xlink:title="label: EntityCentralIndexKey to dei_EntityCentralIndexKey" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityFileNumber" xlink:label="EntityFileNumber" xlink:title="EntityFileNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFileNumber" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFileNumber" xml:lang="en-US" id="dei_EntityFileNumber">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" xlink:title="label: EntityFileNumber to dei_EntityFileNumber" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityTaxIdentificationNumber" xlink:label="EntityTaxIdentificationNumber" xlink:title="EntityTaxIdentificationNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityTaxIdentificationNumber" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityTaxIdentificationNumber" xml:lang="en-US" id="dei_EntityTaxIdentificationNumber">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" xlink:title="label: EntityTaxIdentificationNumber to dei_EntityTaxIdentificationNumber" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityIncorporationStateCountryCode" xlink:label="EntityIncorporationStateCountryCode" xlink:title="EntityIncorporationStateCountryCode" />
    <link:label xlink:type="resource" xlink:label="dei_EntityIncorporationStateCountryCode" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityIncorporationStateCountryCode" xml:lang="en-US" id="dei_EntityIncorporationStateCountryCode">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" xlink:title="label: EntityIncorporationStateCountryCode to dei_EntityIncorporationStateCountryCode" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_CurrentFiscalYearEndDate" xlink:label="CurrentFiscalYearEndDate" xlink:title="CurrentFiscalYearEndDate" />
    <link:label xlink:type="resource" xlink:label="dei_CurrentFiscalYearEndDate" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CurrentFiscalYearEndDate" xml:lang="en-US" id="dei_CurrentFiscalYearEndDate">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" xlink:title="label: CurrentFiscalYearEndDate to dei_CurrentFiscalYearEndDate" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityCurrentReportingStatus" xlink:label="EntityCurrentReportingStatus" xlink:title="EntityCurrentReportingStatus" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCurrentReportingStatus" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCurrentReportingStatus" xml:lang="en-US" id="dei_EntityCurrentReportingStatus">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" xlink:title="label: EntityCurrentReportingStatus to dei_EntityCurrentReportingStatus" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityShellCompany" xlink:label="EntityShellCompany" xlink:title="EntityShellCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityShellCompany" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityShellCompany" xml:lang="en-US" id="dei_EntityShellCompany">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" xlink:title="label: EntityShellCompany to dei_EntityShellCompany" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityFilerCategory" xlink:label="EntityFilerCategory" xlink:title="EntityFilerCategory" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFilerCategory" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFilerCategory" xml:lang="en-US" id="dei_EntityFilerCategory">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" xlink:title="label: EntityFilerCategory to dei_EntityFilerCategory" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntitySmallBusiness" xlink:label="EntitySmallBusiness" xlink:title="EntitySmallBusiness" />
    <link:label xlink:type="resource" xlink:label="dei_EntitySmallBusiness" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntitySmallBusiness" xml:lang="en-US" id="dei_EntitySmallBusiness">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" xlink:title="label: EntitySmallBusiness to dei_EntitySmallBusiness" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityEmergingGrowthCompany" xlink:label="EntityEmergingGrowthCompany" xlink:title="EntityEmergingGrowthCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityEmergingGrowthCompany" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityEmergingGrowthCompany" xml:lang="en-US" id="dei_EntityEmergingGrowthCompany">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" xlink:title="label: EntityEmergingGrowthCompany to dei_EntityEmergingGrowthCompany" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityAddressAddressLine1" xlink:label="EntityAddressAddressLine1" xlink:title="EntityAddressAddressLine1" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressAddressLine1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressAddressLine1" xml:lang="en-US" id="dei_EntityAddressAddressLine1">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" xlink:title="label: EntityAddressAddressLine1 to dei_EntityAddressAddressLine1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityAddressCityOrTown" xlink:label="EntityAddressCityOrTown" xlink:title="EntityAddressCityOrTown" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressCityOrTown" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressCityOrTown" xml:lang="en-US" id="dei_EntityAddressCityOrTown">Entity Address, City or Town</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressCityOrTown" xlink:to="dei_EntityAddressCityOrTown" xlink:title="label: EntityAddressCityOrTown to dei_EntityAddressCityOrTown" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityAddressStateOrProvince" xlink:label="EntityAddressStateOrProvince" xlink:title="EntityAddressStateOrProvince" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressStateOrProvince" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressStateOrProvince" xml:lang="en-US" id="dei_EntityAddressStateOrProvince">Entity Address, State or Province</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressStateOrProvince" xlink:to="dei_EntityAddressStateOrProvince" xlink:title="label: EntityAddressStateOrProvince to dei_EntityAddressStateOrProvince" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityAddressPostalZipCode" xlink:label="EntityAddressPostalZipCode" xlink:title="EntityAddressPostalZipCode" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressPostalZipCode" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressPostalZipCode" xml:lang="en-US" id="dei_EntityAddressPostalZipCode">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" xlink:title="label: EntityAddressPostalZipCode to dei_EntityAddressPostalZipCode" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_CityAreaCode" xlink:label="CityAreaCode" xlink:title="CityAreaCode" />
    <link:label xlink:type="resource" xlink:label="dei_CityAreaCode" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CityAreaCode" xml:lang="en-US" id="dei_CityAreaCode">City Area Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CityAreaCode" xlink:to="dei_CityAreaCode" xlink:title="label: CityAreaCode to dei_CityAreaCode" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_LocalPhoneNumber" xlink:label="LocalPhoneNumber" xlink:title="LocalPhoneNumber" />
    <link:label xlink:type="resource" xlink:label="dei_LocalPhoneNumber" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_LocalPhoneNumber" xml:lang="en-US" id="dei_LocalPhoneNumber">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" xlink:title="label: LocalPhoneNumber to dei_LocalPhoneNumber" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_Security12bTitle" xlink:label="Security12bTitle" xlink:title="Security12bTitle" />
    <link:label xlink:type="resource" xlink:label="dei_Security12bTitle" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_Security12bTitle" xml:lang="en-US" id="dei_Security12bTitle">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" xlink:title="label: Security12bTitle to dei_Security12bTitle" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_TradingSymbol" xlink:label="TradingSymbol" xlink:title="TradingSymbol" />
    <link:label xlink:type="resource" xlink:label="dei_TradingSymbol" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_TradingSymbol" xml:lang="en-US" id="dei_TradingSymbol">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" xlink:title="label: TradingSymbol to dei_TradingSymbol" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_SecurityExchangeName" xlink:label="SecurityExchangeName" xlink:title="SecurityExchangeName" />
    <link:label xlink:type="resource" xlink:label="dei_SecurityExchangeName" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_SecurityExchangeName" xml:lang="en-US" id="dei_SecurityExchangeName">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" xlink:title="label: SecurityExchangeName to dei_SecurityExchangeName" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityCommonStockSharesOutstanding" xlink:label="EntityCommonStockSharesOutstanding" xlink:title="EntityCommonStockSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCommonStockSharesOutstanding" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCommonStockSharesOutstanding" xml:lang="en-US" id="dei_EntityCommonStockSharesOutstanding">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" xlink:title="label: EntityCommonStockSharesOutstanding to dei_EntityCommonStockSharesOutstanding" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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-20240630.xsd#ions_AstrazenecaCollaborationsMember" xlink:label="AstrazenecaCollaborationsMember" xlink:title="AstrazenecaCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstrazenecaCollaborationsMember_lbl" xml:lang="en-US" id="ions_AstrazenecaCollaborationsMember_lbl">Collaboration agreements entered into with AstraZeneca PLC.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationsMember" xlink:to="ions_AstrazenecaCollaborationsMember_lbl" xlink:title="label: AstrazenecaCollaborationsMember to ions_AstrazenecaCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AstrazenecaCollaborationsMember_lbl1" xml:lang="en-US" id="ions_AstrazenecaCollaborationsMember_lbl1">AstraZeneca Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationsMember" xlink:to="ions_AstrazenecaCollaborationsMember_lbl1" xlink:title="label: AstrazenecaCollaborationsMember to ions_AstrazenecaCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationsMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AstrazenecaCollaborationsMember" xml:lang="en-US" id="ions_AstrazenecaCollaborationsMember">AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationsMember" xlink:to="ions_AstrazenecaCollaborationsMember" xlink:title="label: AstrazenecaCollaborationsMember to ions_AstrazenecaCollaborationsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:label="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:title="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl" xml:lang="en-US" id="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl">Collaboration agreement entered into with AstraZeneca PLC in July 2015 to discover and develop antisense therapies for treating cardiovascular and metabolic diseases primarily focused on targets in the kidney and renal diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:to="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl" xlink:title="label: AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember to ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl1" xml:lang="en-US" id="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl1">AstraZeneca Collaboration, Cardiovascular, Renal and Metabolic Diseases [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:to="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl1" xlink:title="label: AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember to ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xml:lang="en-US" id="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember">Cardiovascular, Renal and Metabolic Diseases [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:to="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:title="label: AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember to ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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-20240630.xsd#ions_NextPaymentToBeAchieved" xlink:label="NextPaymentToBeAchieved" xlink:title="NextPaymentToBeAchieved" />
    <link:label xlink:type="resource" xlink:label="ions_NextPaymentToBeAchieved_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NextPaymentToBeAchieved_lbl" xml:lang="en-US" id="ions_NextPaymentToBeAchieved_lbl">The next payment to be achieved under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPaymentToBeAchieved" xlink:to="ions_NextPaymentToBeAchieved_lbl" xlink:title="label: NextPaymentToBeAchieved to ions_NextPaymentToBeAchieved_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NextPaymentToBeAchieved_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NextPaymentToBeAchieved_lbl1" xml:lang="en-US" id="ions_NextPaymentToBeAchieved_lbl1">Next payment to be achieved</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPaymentToBeAchieved" xlink:to="ions_NextPaymentToBeAchieved_lbl1" xlink:title="label: NextPaymentToBeAchieved to ions_NextPaymentToBeAchieved_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NextPaymentToBeAchieved" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NextPaymentToBeAchieved" xml:lang="en-US" id="ions_NextPaymentToBeAchieved">Next payment to be achieved</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPaymentToBeAchieved" xlink:to="ions_NextPaymentToBeAchieved" xlink:title="label: NextPaymentToBeAchieved to ions_NextPaymentToBeAchieved" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfCollaborationAgreements" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements">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" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CumulativePaymentsReceived" xml:lang="en-US" id="ions_CumulativePaymentsReceived">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" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_AstraZenecaCollaborationWainuaMember" xlink:label="AstraZenecaCollaborationWainuaMember" xlink:title="AstraZenecaCollaborationWainuaMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaCollaborationWainuaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstraZenecaCollaborationWainuaMember_lbl" xml:lang="en-US" id="ions_AstraZenecaCollaborationWainuaMember_lbl">Collaboration agreement entered into with AstraZeneca PLC in December 2021 to develop and commercialize WAINUA. WAINUA (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="AstraZenecaCollaborationWainuaMember" xlink:to="ions_AstraZenecaCollaborationWainuaMember_lbl" xlink:title="label: AstraZenecaCollaborationWainuaMember to ions_AstraZenecaCollaborationWainuaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaCollaborationWainuaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AstraZenecaCollaborationWainuaMember_lbl1" xml:lang="en-US" id="ions_AstraZenecaCollaborationWainuaMember_lbl1">AstraZeneca Collaboration, WAINUA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaCollaborationWainuaMember" xlink:to="ions_AstraZenecaCollaborationWainuaMember_lbl1" xlink:title="label: AstraZenecaCollaborationWainuaMember to ions_AstraZenecaCollaborationWainuaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaCollaborationWainuaMember" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_AstraZenecaCollaborationWainuaMember" xml:lang="en-US" id="ions_AstraZenecaCollaborationWainuaMember">WAINUA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaCollaborationWainuaMember" xlink:to="ions_AstraZenecaCollaborationWainuaMember" xlink:title="label: AstraZenecaCollaborationWainuaMember to ions_AstraZenecaCollaborationWainuaMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaCollaborationWainuaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AstraZenecaCollaborationWainuaMember_lbl2" xml:lang="en-US" id="ions_AstraZenecaCollaborationWainuaMember_lbl2">WAINUA (Eplontersen) Collaboration with AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaCollaborationWainuaMember" xlink:to="ions_AstraZenecaCollaborationWainuaMember_lbl2" xlink:title="label: AstraZenecaCollaborationWainuaMember to ions_AstraZenecaCollaborationWainuaMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:label="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:title="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl">The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1">Maximum amount of payments receivable over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">Maximum amount of payments receivable over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:title="label: MaximumAmountOfPaymentsReceivableOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl">The maximum amount of development milestone payments to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1">Maximum amount of development milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">Maximum amount of development milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl">The maximum amount of sales milestone payments to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl1">Maximum amount of sales milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">Maximum amount of sales milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:title="label: MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine">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" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfMedicine to ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl">The maximum amount of upfront payments to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration to ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1">Maximum amount of upfront payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration to ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration">Maximum amount of upfront payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:title="label: MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration to ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes0PercentMember" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember">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" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember" />
    <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>
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:label="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:title="LiabilityRelatedToSaleOfFutureRoyaltiesNet" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl">Amount, after accumulated amortization, of the unamortized liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate method.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_ConvertibleSeniorNotes175PercentMember" xlink:label="ConvertibleSeniorNotes175PercentMember" xlink:title="ConvertibleSeniorNotes175PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes175PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes175PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes175PercentMember_lbl">1.75 percent convertible senior notes due June 2028.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.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:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage">One year or less</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" />
    <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>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage">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-20240630.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage">Total</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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:loc xlink:type="locator" xlink:href="ions-20240630.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:loc xlink:type="locator" xlink:href="ions-20240630.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:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_MaximumContractMaturityPeriodRange2" xlink:label="MaximumContractMaturityPeriodRange2" xlink:title="MaximumContractMaturityPeriodRange2" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange2" xlink:to="ions_MaximumContractMaturityPeriodRange2_lbl" xlink:title="label: MaximumContractMaturityPeriodRange2 to ions_MaximumContractMaturityPeriodRange2_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl1">Maximum contract maturity period, range 2</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange2" xlink:to="ions_MaximumContractMaturityPeriodRange2_lbl1" xlink:title="label: MaximumContractMaturityPeriodRange2 to ions_MaximumContractMaturityPeriodRange2_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange2" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2">Maximum contract maturity period, range 2</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange2" xlink:to="ions_MaximumContractMaturityPeriodRange2" xlink:title="label: MaximumContractMaturityPeriodRange2 to ions_MaximumContractMaturityPeriodRange2" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange3_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange3_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3_lbl1">Maximum contract maturity period, range 3</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange3" xlink:to="ions_MaximumContractMaturityPeriodRange3_lbl1" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange3" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3">Maximum contract maturity period, range 3</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange3" xlink:to="ions_MaximumContractMaturityPeriodRange3" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember">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" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl2">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_lbl2" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_ResearchAndDevelopmentRevenueMember" xlink:label="ResearchAndDevelopmentRevenueMember" xlink:title="ResearchAndDevelopmentRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentRevenueMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember_lbl">Revenue from research and development services.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentRevenueMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember_lbl1">Research and Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl1" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueMember" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember">Research and Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_OtherCommercialMember" xlink:label="OtherCommercialMember" xlink:title="OtherCommercialMember" />
    <link:label xlink:type="resource" xlink:label="ions_OtherCommercialMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OtherCommercialMember_lbl" xml:lang="en-US" id="ions_OtherCommercialMember_lbl">Revenue from the sale of other medicines commercially as well as licensing and royalty revenue from other medicines, including TEGSEDI and WAYLIVRA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCommercialMember" xlink:to="ions_OtherCommercialMember_lbl" xlink:title="label: OtherCommercialMember to ions_OtherCommercialMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OtherCommercialMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OtherCommercialMember_lbl1" xml:lang="en-US" id="ions_OtherCommercialMember_lbl1">Other Commercial [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCommercialMember" xlink:to="ions_OtherCommercialMember_lbl1" xlink:title="label: OtherCommercialMember to ions_OtherCommercialMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OtherCommercialMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OtherCommercialMember" xml:lang="en-US" id="ions_OtherCommercialMember">Other Commercial Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCommercialMember" xlink:to="ions_OtherCommercialMember" xlink:title="label: OtherCommercialMember to ions_OtherCommercialMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_WainusRoyaltiesMember" xlink:label="WainusRoyaltiesMember" xlink:title="WainusRoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_WainusRoyaltiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_WainusRoyaltiesMember_lbl" xml:lang="en-US" id="ions_WainusRoyaltiesMember_lbl">Royalty revenues from the sale of WAINUA (eplontersen).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainusRoyaltiesMember" xlink:to="ions_WainusRoyaltiesMember_lbl" xlink:title="label: WainusRoyaltiesMember to ions_WainusRoyaltiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_WainusRoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_WainusRoyaltiesMember_lbl1" xml:lang="en-US" id="ions_WainusRoyaltiesMember_lbl1">WAINUA Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainusRoyaltiesMember" xlink:to="ions_WainusRoyaltiesMember_lbl1" xlink:title="label: WainusRoyaltiesMember to ions_WainusRoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_WainusRoyaltiesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_WainusRoyaltiesMember" xml:lang="en-US" id="ions_WainusRoyaltiesMember">WAINUA Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainusRoyaltiesMember" xlink:to="ions_WainusRoyaltiesMember" xlink:title="label: WainusRoyaltiesMember to ions_WainusRoyaltiesMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_ResearchDevelopmentAndPatentExpense" xlink:label="ResearchDevelopmentAndPatentExpense" xlink:title="ResearchDevelopmentAndPatentExpense" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchDevelopmentAndPatentExpense_lbl" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense_lbl">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.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpense" xlink:to="ions_ResearchDevelopmentAndPatentExpense_lbl" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchDevelopmentAndPatentExpense_lbl1" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense_lbl1">Research, Development and Patent Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpense" xlink:to="ions_ResearchDevelopmentAndPatentExpense_lbl1" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpense" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchDevelopmentAndPatentExpense" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense">Research, development and patent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpense" xlink:to="ions_ResearchDevelopmentAndPatentExpense" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_WainuaJointDevelopmentRevenueMember" xlink:label="WainuaJointDevelopmentRevenueMember" xlink:title="WainuaJointDevelopmentRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_WainuaJointDevelopmentRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_WainuaJointDevelopmentRevenueMember_lbl" xml:lang="en-US" id="ions_WainuaJointDevelopmentRevenueMember_lbl">Joint development revenue for WAINUA (eplontersen).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainuaJointDevelopmentRevenueMember" xlink:to="ions_WainuaJointDevelopmentRevenueMember_lbl" xlink:title="label: WainuaJointDevelopmentRevenueMember to ions_WainuaJointDevelopmentRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_WainuaJointDevelopmentRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_WainuaJointDevelopmentRevenueMember_lbl1" xml:lang="en-US" id="ions_WainuaJointDevelopmentRevenueMember_lbl1">WAINUA Joint Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainuaJointDevelopmentRevenueMember" xlink:to="ions_WainuaJointDevelopmentRevenueMember_lbl1" xlink:title="label: WainuaJointDevelopmentRevenueMember to ions_WainuaJointDevelopmentRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_WainuaJointDevelopmentRevenueMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_WainuaJointDevelopmentRevenueMember" xml:lang="en-US" id="ions_WainuaJointDevelopmentRevenueMember">WAINUA Joint Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainuaJointDevelopmentRevenueMember" xlink:to="ions_WainuaJointDevelopmentRevenueMember" xlink:title="label: WainuaJointDevelopmentRevenueMember to ions_WainuaJointDevelopmentRevenueMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_CommercialMember" xlink:label="CommercialMember" xlink:title="CommercialMember" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CommercialMember_lbl" xml:lang="en-US" id="ions_CommercialMember_lbl">Revenue from the sale of medicines commercially as well as licensing and royalty revenues from other medicines, including SPINRAZA..</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialMember" xlink:to="ions_CommercialMember_lbl" xlink:title="label: CommercialMember to ions_CommercialMember_lbl" />
    <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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CommercialMember" xml:lang="en-US" id="ions_CommercialMember">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" xlink:title="label: CommercialMember to ions_CommercialMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SpinrazaRoyaltiesMember" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember">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" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeAgreementRevenueMember" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember">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" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:label="InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:title="InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" xml:lang="en-US" id="ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl">Amount of interest expense using the effective interest rate method and amortization of issuance costs related to the sale of future royalties.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_NonCashCapitalAndPatentExpenditures" xlink:label="NonCashCapitalAndPatentExpenditures" xlink:title="NonCashCapitalAndPatentExpenditures" />
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:label="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:title="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" />
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_ProceedsFromSaleOfFutureRoyalties" xlink:label="ProceedsFromSaleOfFutureRoyalties" xlink:title="ProceedsFromSaleOfFutureRoyalties" />
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_RoyaltyPayments" xlink:label="RoyaltyPayments" xlink:title="RoyaltyPayments" />
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    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPayments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPayments_lbl1" xml:lang="en-US" id="ions_RoyaltyPayments_lbl1">Royalty Payments</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPayments" xlink:to="ions_RoyaltyPayments_lbl2" xlink:title="label: RoyaltyPayments to ions_RoyaltyPayments_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_EquitySecuritiesPubliclyTradedCompaniesMember" xlink:label="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:title="EquitySecuritiesPubliclyTradedCompaniesMember" />
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl">The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1">Maximum amount of regulatory milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">Maximum amount of regulatory milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember">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" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_BiogenCollaboration2012NeurologyMember" xlink:label="BiogenCollaboration2012NeurologyMember" xlink:title="BiogenCollaboration2012NeurologyMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2012NeurologyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaboration2012NeurologyMember_lbl" xml:lang="en-US" id="ions_BiogenCollaboration2012NeurologyMember_lbl">Collaborative agreement entered into with Biogen Inc. in December 2012 focused on developing and commercializing novel antisense drugs for up to three targets to treat neurological or neuromuscular diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2012NeurologyMember" xlink:to="ions_BiogenCollaboration2012NeurologyMember_lbl" xlink:title="label: BiogenCollaboration2012NeurologyMember to ions_BiogenCollaboration2012NeurologyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2012NeurologyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaboration2012NeurologyMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaboration2012NeurologyMember_lbl1">Biogen Collaboration, 2012 Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2012NeurologyMember" xlink:to="ions_BiogenCollaboration2012NeurologyMember_lbl1" xlink:title="label: BiogenCollaboration2012NeurologyMember to ions_BiogenCollaboration2012NeurologyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2012NeurologyMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaboration2012NeurologyMember" xml:lang="en-US" id="ions_BiogenCollaboration2012NeurologyMember">2012 Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2012NeurologyMember" xlink:to="ions_BiogenCollaboration2012NeurologyMember" xlink:title="label: BiogenCollaboration2012NeurologyMember to ions_BiogenCollaboration2012NeurologyMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaborationsMember" xml:lang="en-US" id="ions_BiogenCollaborationsMember">Biogen [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" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_IonisMaptMember" xlink:label="IonisMaptMember" xlink:title="IonisMaptMember" />
    <link:label xlink:type="resource" xlink:label="ions_IonisMaptMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IonisMaptMember_lbl" xml:lang="en-US" id="ions_IonisMaptMember_lbl">IONIS-MAPT is an antisense drug designed to selectively reduce the production of microtubule-associated protein tau (MAPT), or tau protein, in the brain, for the treatment of Alzheimer's disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisMaptMember" xlink:to="ions_IonisMaptMember_lbl" xlink:title="label: IonisMaptMember to ions_IonisMaptMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IonisMaptMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IonisMaptMember_lbl1" xml:lang="en-US" id="ions_IonisMaptMember_lbl1">Ionis-Mapt [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisMaptMember" xlink:to="ions_IonisMaptMember_lbl1" xlink:title="label: IonisMaptMember to ions_IonisMaptMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IonisMaptMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IonisMaptMember" xml:lang="en-US" id="ions_IonisMaptMember">IONIS-MAPT [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisMaptMember" xlink:to="ions_IonisMaptMember" xlink:title="label: IonisMaptMember to ions_IonisMaptMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_Ion582Member" xlink:label="Ion582Member" xlink:title="Ion582Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion582Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion582Member_lbl" xml:lang="en-US" id="ions_Ion582Member_lbl">ION582 is an antisense investigational medicine that targets Ubiquitin Protein Ligase E3A-Antisense Transcript (UBE3A-ATS), which is a long non-coding ribonucleic acid (lncRNA).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion582Member" xlink:to="ions_Ion582Member_lbl" xlink:title="label: Ion582Member to ions_Ion582Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion582Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion582Member_lbl1" xml:lang="en-US" id="ions_Ion582Member_lbl1">ION582 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion582Member" xlink:to="ions_Ion582Member_lbl1" xlink:title="label: Ion582Member to ions_Ion582Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion582Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion582Member" xml:lang="en-US" id="ions_Ion582Member">ION582 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion582Member" xlink:to="ions_Ion582Member" xlink:title="label: Ion582Member to ions_Ion582Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_QalsodyMember" xlink:label="QalsodyMember" xlink:title="QalsodyMember" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_QalsodyMember_lbl" xml:lang="en-US" id="ions_QalsodyMember_lbl">Tofersen (IONIS-SOD1Rx or BIIB067), or QALSODY, is an antisense medicine designed to inhibit the production of superoxide dismutase 1, or SOD1, which is a well understood genetic cause of familial amyotrophic lateral sclerosis, or ALS.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyMember" xlink:to="ions_QalsodyMember_lbl" xlink:title="label: QalsodyMember to ions_QalsodyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_QalsodyMember_lbl1" xml:lang="en-US" id="ions_QalsodyMember_lbl1">QALSODY [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyMember" xlink:to="ions_QalsodyMember_lbl1" xlink:title="label: QalsodyMember to ions_QalsodyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_QalsodyMember" xml:lang="en-US" id="ions_QalsodyMember">QALSODY [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyMember" xlink:to="ions_QalsodyMember" xlink:title="label: QalsodyMember to ions_QalsodyMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_OtsukaPharmaceuticalCoLtdCollaborationMember" xlink:label="OtsukaPharmaceuticalCoLtdCollaborationMember" xlink:title="OtsukaPharmaceuticalCoLtdCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl" xml:lang="en-US" id="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl">Collaboration agreement entered into with Otsuka Pharmaceutical Co., Ltd. (Otsuka) in December 2023 to develop and commercialize donidalorsen, an investigational ligand-conjugated antisense (LICA) medicine designed to target the prekallikrein (PKK) pathway.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtsukaPharmaceuticalCoLtdCollaborationMember" xlink:to="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl" xlink:title="label: OtsukaPharmaceuticalCoLtdCollaborationMember to ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl1" xml:lang="en-US" id="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl1">Otsuka Pharmaceutical Co., Ltd. Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtsukaPharmaceuticalCoLtdCollaborationMember" xlink:to="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl1" xlink:title="label: OtsukaPharmaceuticalCoLtdCollaborationMember to ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OtsukaPharmaceuticalCoLtdCollaborationMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OtsukaPharmaceuticalCoLtdCollaborationMember" xml:lang="en-US" id="ions_OtsukaPharmaceuticalCoLtdCollaborationMember">Otsuka [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtsukaPharmaceuticalCoLtdCollaborationMember" xlink:to="ions_OtsukaPharmaceuticalCoLtdCollaborationMember" xlink:title="label: OtsukaPharmaceuticalCoLtdCollaborationMember to ions_OtsukaPharmaceuticalCoLtdCollaborationMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems">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" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_ConvertibleNotesDisclosureTable" xlink:label="ConvertibleNotesDisclosureTable" xlink:title="ConvertibleNotesDisclosureTable" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureTable_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleNotesDisclosureTable_lbl" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureTable_lbl">Disclosure of information about income taxes.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureTable" xlink:to="ions_ConvertibleNotesDisclosureTable_lbl" xlink:title="label: ConvertibleNotesDisclosureTable to ions_ConvertibleNotesDisclosureTable_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureTable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleNotesDisclosureTable_lbl1" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureTable_lbl1">Convertible Notes Disclosure [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureTable" xlink:to="ions_ConvertibleNotesDisclosureTable_lbl1" xlink:title="label: ConvertibleNotesDisclosureTable to ions_ConvertibleNotesDisclosureTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_ConvertibleNotesDisclosureLineItems" xlink:label="ConvertibleNotesDisclosureLineItems" xlink:title="ConvertibleNotesDisclosureLineItems" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleNotesDisclosureLineItems_lbl" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureLineItems_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="ConvertibleNotesDisclosureLineItems" xlink:to="ions_ConvertibleNotesDisclosureLineItems_lbl" xlink:title="label: ConvertibleNotesDisclosureLineItems to ions_ConvertibleNotesDisclosureLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleNotesDisclosureLineItems_lbl1" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureLineItems_lbl1">Convertible Notes Disclosure [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureLineItems" xlink:to="ions_ConvertibleNotesDisclosureLineItems_lbl1" xlink:title="label: ConvertibleNotesDisclosureLineItems to ions_ConvertibleNotesDisclosureLineItems_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureLineItems" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleNotesDisclosureLineItems" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureLineItems">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureLineItems" xlink:to="ions_ConvertibleNotesDisclosureLineItems" xlink:title="label: ConvertibleNotesDisclosureLineItems to ions_ConvertibleNotesDisclosureLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:label="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:title="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl">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.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:to="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1">Debt Instrument, Convertible, Percentage of principal amount used as purchase price upon occurrence of fundamental change</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:to="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange">Percentage of principal amount used as purchase price upon occurrence of fundamental change</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:to="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1">Debt Instrument, Convertible, Conversion Price including call spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread">Effective conversion price per share with call spread (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_DebtInstrumentConvertibleSharesSubjectToConversion" xlink:label="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:title="DebtInstrumentConvertibleSharesSubjectToConversion" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl">The number of shares of common stock subject to conversion if the debt was converted to equity.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:to="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" xlink:title="label: DebtInstrumentConvertibleSharesSubjectToConversion to ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1">Debt Instrument, Convertible, Shares Subject to Conversion</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:to="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" xlink:title="label: DebtInstrumentConvertibleSharesSubjectToConversion to ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleSharesSubjectToConversion" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentConvertibleSharesSubjectToConversion" xml:lang="en-US" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion">Total shares of common stock subject to conversion (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:to="ions_DebtInstrumentConvertibleSharesSubjectToConversion" xlink:title="label: DebtInstrumentConvertibleSharesSubjectToConversion to ions_DebtInstrumentConvertibleSharesSubjectToConversion" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_CallSpread" xlink:label="CallSpread" xlink:title="CallSpread" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CallSpread_lbl" xml:lang="en-US" id="ions_CallSpread_lbl">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.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread_lbl" xlink:title="label: CallSpread to ions_CallSpread_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CallSpread_lbl1" xml:lang="en-US" id="ions_CallSpread_lbl1">Call Spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread_lbl1" xlink:title="label: CallSpread to ions_CallSpread_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CallSpread" xml:lang="en-US" id="ions_CallSpread">Cost of call spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread" xlink:title="label: CallSpread to ions_CallSpread" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_SupplementalFinancialDataAbstract" xlink:label="SupplementalFinancialDataAbstract" xlink:title="SupplementalFinancialDataAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_SupplementalFinancialDataAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SupplementalFinancialDataAbstract_lbl1" xml:lang="en-US" id="ions_SupplementalFinancialDataAbstract_lbl1">Supplemental Financial Data [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SupplementalFinancialDataAbstract" xlink:to="ions_SupplementalFinancialDataAbstract_lbl1" xlink:title="label: SupplementalFinancialDataAbstract to ions_SupplementalFinancialDataAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ClinicalRawMaterialsMember" xml:lang="en-US" id="ions_ClinicalRawMaterialsMember">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" xlink:title="label: ClinicalRawMaterialsMember to ions_ClinicalRawMaterialsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CommercialRawMaterialsMember" xml:lang="en-US" id="ions_CommercialRawMaterialsMember">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" xlink:title="label: CommercialRawMaterialsMember to ions_CommercialRawMaterialsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedClinicalDevelopmentExpenses" xml:lang="en-US" id="ions_AccruedClinicalDevelopmentExpenses">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" xlink:title="label: AccruedClinicalDevelopmentExpenses to ions_AccruedClinicalDevelopmentExpenses" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedInLicensingFeesCurrent" xml:lang="en-US" id="ions_AccruedInLicensingFeesCurrent">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" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" />
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_GrantedIn2023Member" xlink:label="GrantedIn2023Member" xlink:title="GrantedIn2023Member" />
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_ResearchDevelopmentAndPatentExpensesMember" xlink:label="ResearchDevelopmentAndPatentExpensesMember" xlink:title="ResearchDevelopmentAndPatentExpensesMember" />
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_GrantedIn2024Member" xlink:label="GrantedIn2024Member" xlink:title="GrantedIn2024Member" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedIn2024Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GrantedIn2024Member_lbl" xml:lang="en-US" id="ions_GrantedIn2024Member_lbl">Awards granted in 2024.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_GrantedIn2024Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GrantedIn2024Member_lbl1" xml:lang="en-US" id="ions_GrantedIn2024Member_lbl1">Granted in 2024 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedIn2024Member" xlink:to="ions_GrantedIn2024Member_lbl1" xlink:title="label: GrantedIn2024Member to ions_GrantedIn2024Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedIn2024Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GrantedIn2024Member" xml:lang="en-US" id="ions_GrantedIn2024Member">Granted in 2024 [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:label="AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:title="AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" xml:lang="en-US" id="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl">Amount of amortization expense attributable to the sale of future royalties.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" xml:lang="en-US" id="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1">Amortization of Issuance Costs Related to Sale of Future Royalties</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xml:lang="en-US" id="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties">Amortization of issuance costs related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:title="label: AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties to ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_RoyaltyPurchaseAgreementMember" xlink:label="RoyaltyPurchaseAgreementMember" xlink:title="RoyaltyPurchaseAgreementMember" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPurchaseAgreementMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPurchaseAgreementMember_lbl" xml:lang="en-US" id="ions_RoyaltyPurchaseAgreementMember_lbl">In January 2023, the Company entered into a royalty purchase agreement with Royalty Pharma to monetize a portion of future SPINRAZA and pelacarsen royalties the Company is entitled to under arrangements with Biogen and Novartis, respectively.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPurchaseAgreementMember" xlink:to="ions_RoyaltyPurchaseAgreementMember_lbl" xlink:title="label: RoyaltyPurchaseAgreementMember to ions_RoyaltyPurchaseAgreementMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPurchaseAgreementMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPurchaseAgreementMember_lbl1" xml:lang="en-US" id="ions_RoyaltyPurchaseAgreementMember_lbl1">Royalty Purchase Agreement [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPurchaseAgreementMember" xlink:to="ions_RoyaltyPurchaseAgreementMember_lbl1" xlink:title="label: RoyaltyPurchaseAgreementMember to ions_RoyaltyPurchaseAgreementMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPurchaseAgreementMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPurchaseAgreementMember" xml:lang="en-US" id="ions_RoyaltyPurchaseAgreementMember">Royalty Purchase Agreement [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPurchaseAgreementMember" xlink:to="ions_RoyaltyPurchaseAgreementMember" xlink:title="label: RoyaltyPurchaseAgreementMember to ions_RoyaltyPurchaseAgreementMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_SpinrazaMember" xlink:label="SpinrazaMember" xlink:title="SpinrazaMember" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SpinrazaMember_lbl" xml:lang="en-US" id="ions_SpinrazaMember_lbl">Nusinersen, marketed as Spinraza, is a medicine used in treating spinal muscular atrophy (SMA), a progressive, debilitating and often fatal genetic disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaMember" xlink:to="ions_SpinrazaMember_lbl" xlink:title="label: SpinrazaMember to ions_SpinrazaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SpinrazaMember_lbl1" xml:lang="en-US" id="ions_SpinrazaMember_lbl1">SPINRAZA [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_SpinrazaMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SpinrazaMember" xml:lang="en-US" id="ions_SpinrazaMember">SPINRAZA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaMember" xlink:to="ions_SpinrazaMember" xlink:title="label: SpinrazaMember to ions_SpinrazaMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_PelacarsenMember" xlink:label="PelacarsenMember" xlink:title="PelacarsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PelacarsenMember_lbl" xml:lang="en-US" id="ions_PelacarsenMember_lbl">Pelacarsen, also known as IONIS-APO(a)-L, AKCEA-APO(a)-L, and TQJ230, is an investigational antisense medicine designed to reduce apolipoprotein(a) in the liver in patients suffering from high levels of the lipoprotein Lp(a).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenMember" xlink:to="ions_PelacarsenMember_lbl" xlink:title="label: PelacarsenMember to ions_PelacarsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PelacarsenMember_lbl1" xml:lang="en-US" id="ions_PelacarsenMember_lbl1">Pelacarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenMember" xlink:to="ions_PelacarsenMember_lbl1" xlink:title="label: PelacarsenMember to ions_PelacarsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PelacarsenMember" xml:lang="en-US" id="ions_PelacarsenMember">Pelacarsen [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_RoyaltyRevenueMonetizationAbstract" xlink:label="RoyaltyRevenueMonetizationAbstract" xlink:title="RoyaltyRevenueMonetizationAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyRevenueMonetizationAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyRevenueMonetizationAbstract_lbl1" xml:lang="en-US" id="ions_RoyaltyRevenueMonetizationAbstract_lbl1">Royalty Revenue Monetization [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_RoyaltyRevenueMonetizationAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyRevenueMonetizationAbstract" xml:lang="en-US" id="ions_RoyaltyRevenueMonetizationAbstract">Royalty Revenue Monetization [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyRevenueMonetizationAbstract" xlink:to="ions_RoyaltyRevenueMonetizationAbstract" xlink:title="label: RoyaltyRevenueMonetizationAbstract to ions_RoyaltyRevenueMonetizationAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:label="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:title="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl" xml:lang="en-US" id="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl">The maximum amount of annual sales on which royalty payments are paid under the royalty purchase agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:to="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl" xlink:title="label: MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid to ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1">Maximum amount of annual sales on which royalty payments are paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:to="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1" xlink:title="label: MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid to ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xml:lang="en-US" id="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid">Maximum amount of annual sales on which royalty payments are paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:to="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:title="label: MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid to ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForAdditionalMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForAdditionalMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl">The maximum amount of payments receivable for additional milestones under the royalty purchase agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForAdditionalMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForAdditionalMilestones to ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1">Maximum amount of payments receivable for additional milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForAdditionalMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForAdditionalMilestones to ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_UpfrontRoyaltyPaymentReceived" xlink:label="UpfrontRoyaltyPaymentReceived" xlink:title="UpfrontRoyaltyPaymentReceived" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontRoyaltyPaymentReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontRoyaltyPaymentReceived_lbl" xml:lang="en-US" id="ions_UpfrontRoyaltyPaymentReceived_lbl">The amount of upfront payments received during the period under the royalty purchase agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontRoyaltyPaymentReceived" xlink:to="ions_UpfrontRoyaltyPaymentReceived_lbl" xlink:title="label: UpfrontRoyaltyPaymentReceived to ions_UpfrontRoyaltyPaymentReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontRoyaltyPaymentReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontRoyaltyPaymentReceived_lbl1" xml:lang="en-US" id="ions_UpfrontRoyaltyPaymentReceived_lbl1">Upfront royalty payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontRoyaltyPaymentReceived" xlink:to="ions_UpfrontRoyaltyPaymentReceived_lbl1" xlink:title="label: UpfrontRoyaltyPaymentReceived to ions_UpfrontRoyaltyPaymentReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontRoyaltyPaymentReceived" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpfrontRoyaltyPaymentReceived" xml:lang="en-US" id="ions_UpfrontRoyaltyPaymentReceived">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontRoyaltyPaymentReceived" xlink:to="ions_UpfrontRoyaltyPaymentReceived" xlink:title="label: UpfrontRoyaltyPaymentReceived to ions_UpfrontRoyaltyPaymentReceived" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:label="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:title="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl" xml:lang="en-US" id="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl">Maximum royalty payments under the royalty purchase agreement made before royalty interest reverts back to the Company.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:to="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl" xlink:title="label: MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack to ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1" xml:lang="en-US" id="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1">Maximum royalty payments made before royalty interest reverts back</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:to="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1" xlink:title="label: MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack to ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xml:lang="en-US" id="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack">Maximum royalty payments made before royalty interest reverts back</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:to="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:title="label: MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack to ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.xsd#ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:label="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:title="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl" xml:lang="en-US" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl">The percentage of royalty payments paid on annual sales of medicine.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:to="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl" xlink:title="label: PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine to ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1" xml:lang="en-US" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1">Percentage of royalty payments paid on annual sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:to="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1" xlink:title="label: PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine to ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xml:lang="en-US" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine">Percentage of royalty payments paid on annual sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:to="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:title="label: PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine to ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_LicensingAndOtherRoyaltiesMember" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember">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" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpfrontPaymentReceived" xml:lang="en-US" id="ions_UpfrontPaymentReceived">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" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfMaterialComponents" xml:lang="en-US" id="ions_NumberOfMaterialComponents">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" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice">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" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice" />
    <link:loc xlink:type="locator" xlink:href="ions-20240630.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" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">Number of 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" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" />
    <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-20240630.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>
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<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492877267984">
<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">6 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jul. 26, 2024</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>
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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_AmendmentFlag', window );">Amendment Flag</a></td>
<td class="text">false<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_DocumentQuarterlyReport', window );">Document Quarterly Report</a></td>
<td class="text">true<span></span>
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<td class="text">&#160;<span></span>
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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_DocumentPeriodEndDate', window );">Document Period End Date</a></td>
<td class="text">Jun. 30,  2024<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">2024<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">Q2<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_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>
</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_EntityTaxIdentificationNumber', window );">Entity Tax Identification Number</a></td>
<td class="text">33-0336973<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_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>
</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_EntityAddressCityOrTown', window );">Entity Address, City or Town</a></td>
<td class="text">Carlsbad<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_EntityAddressStateOrProvince', window );">Entity Address, State or Province</a></td>
<td class="text">CA<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_EntityAddressPostalZipCode', window );">Entity Address, Postal Zip Code</a></td>
<td class="text">92010<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_CityAreaCode', window );">City Area Code</a></td>
<td class="text">760<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_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>
</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_TradingSymbol', window );">Trading Symbol</a></td>
<td class="text">IONS<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_SecurityExchangeName', window );">Security Exchange Name</a></td>
<td class="text">NASDAQ<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_EntityCurrentReportingStatus', window );">Entity Current Reporting Status</a></td>
<td class="text">Yes<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_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>
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<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>
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<td class="text">&#160;<span></span>
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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>
</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_EntityCommonStockSharesOutstanding', window );">Entity Common Stock, Shares Outstanding</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">146,211,091<span></span>
</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>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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<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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<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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
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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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<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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<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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<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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
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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_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>14
<FILENAME>R2.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492879564272">
<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>Jun. 30, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</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">$ 293,993<span></span>
</td>
<td class="nump">$ 399,266<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">1,784,693<span></span>
</td>
<td class="nump">1,931,935<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">27,259<span></span>
</td>
<td class="nump">97,778<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">28,723<span></span>
</td>
<td class="nump">28,425<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">194,715<span></span>
</td>
<td class="nump">184,449<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">2,329,383<span></span>
</td>
<td class="nump">2,641,853<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">75,902<span></span>
</td>
<td class="nump">71,043<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_OperatingLeaseRightOfUseAsset', window );">Right-of-use assets</a></td>
<td class="nump">166,939<span></span>
</td>
<td class="nump">171,896<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">118,904<span></span>
</td>
<td class="nump">105,280<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">2,691,128<span></span>
</td>
<td class="nump">2,990,072<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">9,243<span></span>
</td>
<td class="nump">26,027<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">35,018<span></span>
</td>
<td class="nump">67,727<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">114,330<span></span>
</td>
<td class="nump">147,894<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">284<span></span>
</td>
<td class="nump">2,151<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_ConvertibleDebtCurrent', window );">0.125 percent convertible senior notes, net</a></td>
<td class="nump">44,422<span></span>
</td>
<td class="nump">44,332<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">94,066<span></span>
</td>
<td class="nump">151,128<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_OtherLiabilitiesCurrent', window );">Other current liabilities</a></td>
<td class="nump">8,799<span></span>
</td>
<td class="nump">8,831<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_LiabilitiesCurrent', window );">Total current liabilities</a></td>
<td class="nump">306,162<span></span>
</td>
<td class="nump">448,090<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_ContractWithCustomerLiabilityNoncurrent', window );">Long-term deferred contract revenue</a></td>
<td class="nump">188,701<span></span>
</td>
<td class="nump">241,184<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_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Liability related to sale of future royalties, net</a></td>
<td class="nump">533,754<span></span>
</td>
<td class="nump">513,736<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_OperatingLeaseLiabilityNoncurrent', window );">Long-term lease liabilities</a></td>
<td class="nump">166,438<span></span>
</td>
<td class="nump">170,875<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_OtherLiabilitiesNoncurrent', window );">Long-term obligations</a></td>
<td class="nump">41,773<span></span>
</td>
<td class="nump">41,836<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">2,427,430<span></span>
</td>
<td class="nump">2,603,386<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, 146,025,246 and 144,340,526 shares issued and outstanding at June 30, 2024 (unaudited) and December 31, 2023, respectively</a></td>
<td class="nump">146<span></span>
</td>
<td class="nump">144<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">2,303,369<span></span>
</td>
<td class="nump">2,215,098<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">(34,838)<span></span>
</td>
<td class="num">(32,645)<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">(2,004,979)<span></span>
</td>
<td class="num">(1,795,911)<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">263,698<span></span>
</td>
<td class="nump">386,686<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">2,691,128<span></span>
</td>
<td class="nump">2,990,072<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_ConvertibleSeniorNotes175PercentMember', window );">1.75 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">563,647<span></span>
</td>
<td class="nump">562,285<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="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">$ 626,955<span></span>
</td>
<td class="nump">$ 625,380<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 the unamortized liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate 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_LiabilityRelatedToSaleOfFutureRoyaltiesNet</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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(19)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(15)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<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;">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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">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>Amount, after tax, of accumulated increase (decrease) in equity from transaction and other event and circumstance from nonowner source.</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> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-14A<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-11<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480016/944-40-65-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (h)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480016/944-40-65-2<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-14<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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">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>Amount of asset recognized for present right to economic benefit.</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_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>Amount of asset recognized for present right to economic benefit, 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> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (bb)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481203/810-10-50-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481231/810-10-45-25<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 4: 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210.13-02(a)(4)(iii)(B))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480097/470-10-S99-1B<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480097/470-10-S99-1B<br><br>Reference 19: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480097/470-10-S99-1B<br><br>Reference 20: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481404/852-10-50-7<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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483467/210-10-45-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-4<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://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(22))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<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;">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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<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;">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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<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;">us-gaap_ContractWithCustomerLiabilityNoncurrent</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>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConvertibleDebtCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 the carrying value of long-term convertible debt as of the balance sheet date that is scheduled to be repaid within one year or in the normal operating cycle if longer. Convertible debt is a financial 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(19))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">us-gaap_ConvertibleDebtCurrent</td>
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<tr>
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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>
<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_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> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">us-gaap_ConvertibleDebtNoncurrent</td>
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<tr>
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<td><strong> Balance Type:</strong></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 );">- 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">us-gaap_EmployeeRelatedLiabilitiesCurrent</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>
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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_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/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483467/210-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">us-gaap_InventoryNet</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>instant</td>
</tr>
</table></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 );">- Definition</a><div><p>Amount of liability recognized for present obligation requiring transfer or otherwise providing economic benefit to others.</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_Liabilities</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:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</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_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/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(25))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 323<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481687/323-10-50-3<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-28<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(23))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(32))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">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://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(21))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481203/810-10-50-3<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481231/810-10-45-25<br><br>Reference 4: 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-URI https://asc.fasb.org/1943274/2147480097/470-10-S99-1B<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480097/470-10-S99-1B<br><br>Reference 19: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480097/470-10-S99-1B<br><br>Reference 20: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481404/852-10-50-7<br><br>Reference 21: 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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_OperatingLeaseLiabilityNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Present value of lessee's discounted obligation for lease payments from operating lease, 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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479041/842-20-45-1<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;">us-gaap_OperatingLeaseLiabilityNoncurrent</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_OperatingLeaseRightOfUseAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 lessee's right to use underlying asset under 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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479041/842-20-45-1<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;">us-gaap_OperatingLeaseRightOfUseAsset</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_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/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(17))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">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_OtherLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<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_OtherLiabilitiesCurrent</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_OtherLiabilitiesNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 classified as other, due after 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(24))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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>
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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 );">- 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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 360<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482099/360-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7A<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478964/842-20-50-7A<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 360<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478451/942-360-50-1<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>
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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 of accumulated undistributed earnings (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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480016/944-40-65-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (h)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480016/944-40-65-2<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480990/946-20-50-11<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(17))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br><br>Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480008/505-10-S99-1<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;">us-gaap_RetainedEarningsAccumulatedDeficit</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>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> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(5))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">us-gaap_ShortTermInvestments</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:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</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>Amount of equity (deficit) attributable to parent. Excludes temporary equity and equity 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://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(31))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 5: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 946<br> -SubTopic 830<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479168/946-830-55-12<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(19))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.6-05(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-2<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(7))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 11: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 12: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 323<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481687/323-10-50-3<br><br>Reference 13: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-28<br><br>Reference 14: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 310<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 4.E)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480418/310-10-S99-2<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;">us-gaap_StockholdersEquity</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>
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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>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882140704">
<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>Jun. 30, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</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">146,025,246<span></span>
</td>
<td class="nump">144,340,526<span></span>
</td>
</tr>
<tr class="re">
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<td class="nump">146,025,246<span></span>
</td>
<td class="nump">144,340,526<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_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</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_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>
</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_ConvertibleSeniorNotes175PercentMember', window );">1.75 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>
</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="nump">1.75%<span></span>
</td>
<td class="nump">1.75%<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="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>
</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">0.00%<span></span>
</td>
<td class="nump">0.00%<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_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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">us-gaap_CommonStockParOrStatedValuePerShare</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
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<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_CommonStockSharesAuthorized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<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;">us-gaap_CommonStockSharesAuthorized</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>
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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_CommonStockSharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">us-gaap_CommonStockSharesIssued</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:sharesItemType</td>
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<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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481112/505-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.6-05(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-2<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br><br>Reference 6: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(7))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<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>
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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>xbrli:sharesItemType</td>
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<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
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<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://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<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 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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</tr>
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<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>
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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_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>
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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_ConvertibleSeniorNotes0125PercentMember">
<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_ConvertibleSeniorNotes0125PercentMember</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> Balance Type:</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 );">- 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_ConvertibleSeniorNotes175PercentMember</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 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>
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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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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492879918512">
<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">6 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</div></th>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</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_RevenueFromContractWithCustomerAbstract', 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>
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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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 225,250<span></span>
</td>
<td class="nump">$ 188,411<span></span>
</td>
<td class="nump">$ 344,748<span></span>
</td>
<td class="nump">$ 318,935<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">4,164<span></span>
</td>
<td class="nump">2,537<span></span>
</td>
<td class="nump">6,314<span></span>
</td>
<td class="nump">3,880<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">222,064<span></span>
</td>
<td class="nump">229,927<span></span>
</td>
<td class="nump">436,280<span></span>
</td>
<td class="nump">427,740<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">65,113<span></span>
</td>
<td class="nump">46,142<span></span>
</td>
<td class="nump">117,758<span></span>
</td>
<td class="nump">91,658<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">291,341<span></span>
</td>
<td class="nump">278,606<span></span>
</td>
<td class="nump">560,352<span></span>
</td>
<td class="nump">523,278<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">(66,091)<span></span>
</td>
<td class="num">(90,195)<span></span>
</td>
<td class="num">(215,604)<span></span>
</td>
<td class="num">(204,343)<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</a></td>
<td class="nump">25,599<span></span>
</td>
<td class="nump">20,792<span></span>
</td>
<td class="nump">51,884<span></span>
</td>
<td class="nump">39,419<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">(4,490)<span></span>
</td>
<td class="num">(2,291)<span></span>
</td>
<td class="num">(8,641)<span></span>
</td>
<td class="num">(3,899)<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_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties', window );">Interest expense related to sale of future royalties</a></td>
<td class="num">(18,296)<span></span>
</td>
<td class="num">(17,655)<span></span>
</td>
<td class="num">(36,254)<span></span>
</td>
<td class="num">(33,170)<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_GainLossOnInvestments', window );">Gain (loss) on investments</a></td>
<td class="num">(3,533)<span></span>
</td>
<td class="nump">718<span></span>
</td>
<td class="num">(1,200)<span></span>
</td>
<td class="nump">189<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_OtherNonoperatingIncomeExpense', window );">Other income</a></td>
<td class="nump">610<span></span>
</td>
<td class="nump">11,183<span></span>
</td>
<td class="nump">887<span></span>
</td>
<td class="nump">11,414<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_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest', window );">Loss before income tax expense</a></td>
<td class="num">(66,201)<span></span>
</td>
<td class="num">(77,448)<span></span>
</td>
<td class="num">(208,928)<span></span>
</td>
<td class="num">(190,390)<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_IncomeTaxExpenseBenefit', window );">Income tax expense</a></td>
<td class="num">(64)<span></span>
</td>
<td class="num">(7,842)<span></span>
</td>
<td class="num">(140)<span></span>
</td>
<td class="num">(19,223)<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_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (66,265)<span></span>
</td>
<td class="num">$ (85,290)<span></span>
</td>
<td class="num">$ (209,068)<span></span>
</td>
<td class="num">$ (209,613)<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_EarningsPerShareBasic', window );">Basic net loss per share (in dollars per share)</a></td>
<td class="num">$ (0.45)<span></span>
</td>
<td class="num">$ (0.6)<span></span>
</td>
<td class="num">$ (1.43)<span></span>
</td>
<td class="num">$ (1.47)<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_EarningsPerShareDiluted', window );">Diluted net loss per share (in dollars per share)</a></td>
<td class="num">$ (0.45)<span></span>
</td>
<td class="num">$ (0.6)<span></span>
</td>
<td class="num">$ (1.43)<span></span>
</td>
<td class="num">$ (1.47)<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_WeightedAverageNumberOfSharesOutstandingBasic', window );">Shares used in computing basic net loss per share (in shares)</a></td>
<td class="nump">145,958<span></span>
</td>
<td class="nump">143,098<span></span>
</td>
<td class="nump">145,748<span></span>
</td>
<td class="nump">142,918<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_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net loss per share (in shares)</a></td>
<td class="nump">145,958<span></span>
</td>
<td class="nump">143,098<span></span>
</td>
<td class="nump">145,748<span></span>
</td>
<td class="nump">142,918<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="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:</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">$ 72,036<span></span>
</td>
<td class="nump">$ 77,897<span></span>
</td>
<td class="nump">$ 131,629<span></span>
</td>
<td class="nump">$ 145,664<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="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:</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">56,743<span></span>
</td>
<td class="nump">61,012<span></span>
</td>
<td class="nump">95,198<span></span>
</td>
<td class="nump">111,258<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_WainusRoyaltiesMember', window );">WAINUA 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_RevenueFromContractWithCustomerAbstract', 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">3,781<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">4,907<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_srt_ProductOrServiceAxis=ions_OtherCommercialMember', window );">Other 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_RevenueFromContractWithCustomerAbstract', 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">11,512<span></span>
</td>
<td class="nump">16,885<span></span>
</td>
<td class="nump">31,524<span></span>
</td>
<td class="nump">34,406<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="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:</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">153,214<span></span>
</td>
<td class="nump">110,514<span></span>
</td>
<td class="nump">213,119<span></span>
</td>
<td class="nump">173,271<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="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:</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">141,524<span></span>
</td>
<td class="nump">91,013<span></span>
</td>
<td class="nump">190,870<span></span>
</td>
<td class="nump">129,347<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_WainuaJointDevelopmentRevenueMember', window );">WAINUA 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="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:</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">$ 11,690<span></span>
</td>
<td class="nump">$ 19,501<span></span>
</td>
<td class="nump">$ 22,249<span></span>
</td>
<td class="nump">$ 43,924<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 interest expense using the effective interest rate method and amortization of issuance costs related to the sale of future royalties.</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_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties</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_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://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(2)(d))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(2)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<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;">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>
</table>
<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> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<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;">us-gaap_CostsAndExpenses</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: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>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_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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<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_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> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-6<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 52<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482635/260-10-55-52<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 805<br> -SubTopic 60<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (g)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147476176/805-60-65-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 323<br> -Name 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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/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-6<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 52<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482635/260-10-55-52<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 805<br> -SubTopic 60<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (g)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147476176/805-60-65-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 323<br> -Name 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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_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> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(9)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(7)(c))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 3: http://www.xbrl.org/2003/role/recommendedDisclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 48<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-48<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 6: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(11))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 9: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 31<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-31<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 235<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-05(b)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477314/942-235-S99-1<br><br>Reference 11: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(10))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 12: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(15))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478524/942-220-S99-1<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;">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> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-9<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479360/740-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-8<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-10<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -SubTopic 20<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482659/740-20-45-2<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -SubTopic 10<br> -Topic 235<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<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;">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 interest expense classified as operating and nonoperating. Includes, but is not limited to, cost of borrowing 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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 48<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-48<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 49<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-49<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-24<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483013/835-20-50-1<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;">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> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(7)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(7)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<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;">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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-6<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-9<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 805<br> -SubTopic 60<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (g)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147476176/805-60-65-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 323<br> -Name 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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>
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<tr>
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<td>xbrli:monetaryItemType</td>
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<td><strong> Balance 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_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>
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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>xbrli:stringItemType</td>
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<tr>
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<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
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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_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>
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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_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> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(9))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<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;">us-gaap_OtherNonoperatingIncomeExpense</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: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_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>
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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>
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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_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>
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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_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_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> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<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;">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> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 16<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482689/260-10-45-16<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> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482689/260-10-45-10<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>
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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>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_CommercialMember">
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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>
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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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<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;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember</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;">srt_ProductOrServiceAxis=ions_CollaborativeAgreementRevenueMember</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 );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_WainuaJointDevelopmentRevenueMember</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;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492876864944">
<tr>
<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">6 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</div></th>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</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>
</td>
<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_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (66,265)<span></span>
</td>
<td class="num">$ (85,290)<span></span>
</td>
<td class="num">$ (209,068)<span></span>
</td>
<td class="num">$ (209,613)<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 );">Unrealized gains (losses) on debt securities, net of tax</a></td>
<td class="nump">150<span></span>
</td>
<td class="num">(2,000)<span></span>
</td>
<td class="num">(2,056)<span></span>
</td>
<td class="nump">6,393<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 );">Currency translation adjustment</a></td>
<td class="num">(24)<span></span>
</td>
<td class="nump">70<span></span>
</td>
<td class="num">(137)<span></span>
</td>
<td class="nump">174<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">$ (66,139)<span></span>
</td>
<td class="num">$ (87,220)<span></span>
</td>
<td class="num">$ (211,261)<span></span>
</td>
<td class="num">$ (203,046)<span></span>
</td>
</tr>
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<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> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(24))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(26))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478524/942-220-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(22))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-1A<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-1B<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-5<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>
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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>credit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</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_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>
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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>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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</table>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after tax and reclassification adjustment, of gain (loss) in value of unsold investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), attributable to 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> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 19<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481231/810-10-45-19<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 20<br> -SubTopic 10<br> -Topic 810<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481231/810-10-45-20<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(3)<br> -SubTopic 10<br> -Topic 810<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481203/810-10-50-1A<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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<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 );">- 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>
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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>
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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_StatementOfIncomeAndComprehensiveIncomeAbstract</td>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492880716720">
<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>
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<td class="nump">$ 142<span></span>
</td>
<td class="nump">$ 2,059,850<span></span>
</td>
<td class="num">$ (57,480)<span></span>
</td>
<td class="num">$ (1,429,625)<span></span>
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</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>
<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">(209,613)<span></span>
</td>
<td class="num">(209,613)<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 gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,393<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,393<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="nump">174<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">174<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">4,949<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">4,950<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">1,109<span></span>
</td>
<td class="text">&#160;<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">53,510<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">53,510<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_StockholdersEquity', window );">Balance at Jun. 30, 2023</a></td>
<td class="nump">$ 143<span></span>
</td>
<td class="nump">2,118,309<span></span>
</td>
<td class="num">(50,913)<span></span>
</td>
<td class="num">(1,639,238)<span></span>
</td>
<td class="nump">428,301<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, 2023</a></td>
<td class="nump">143,167<span></span>
</td>
<td class="text">&#160;<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_StockholdersEquity', window );">Balance at Mar. 31, 2023</a></td>
<td class="nump">$ 143<span></span>
</td>
<td class="nump">2,089,358<span></span>
</td>
<td class="num">(48,983)<span></span>
</td>
<td class="num">(1,553,948)<span></span>
</td>
<td class="nump">486,570<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 Mar. 31, 2023</a></td>
<td class="nump">143,023<span></span>
</td>
<td class="text">&#160;<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">(85,290)<span></span>
</td>
<td class="num">(85,290)<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 gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(2,000)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(2,000)<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="nump">70<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">70<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">2,390<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">2,390<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">144<span></span>
</td>
<td class="text">&#160;<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">26,561<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">26,561<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_StockholdersEquity', window );">Balance at Jun. 30, 2023</a></td>
<td class="nump">$ 143<span></span>
</td>
<td class="nump">2,118,309<span></span>
</td>
<td class="num">(50,913)<span></span>
</td>
<td class="num">(1,639,238)<span></span>
</td>
<td class="nump">428,301<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, 2023</a></td>
<td class="nump">143,167<span></span>
</td>
<td class="text">&#160;<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_StockholdersEquity', window );">Balance at Dec. 31, 2023</a></td>
<td class="nump">$ 144<span></span>
</td>
<td class="nump">2,215,098<span></span>
</td>
<td class="num">(32,645)<span></span>
</td>
<td class="num">(1,795,911)<span></span>
</td>
<td class="nump">386,686<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, 2023</a></td>
<td class="nump">144,341<span></span>
</td>
<td class="text">&#160;<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">(209,068)<span></span>
</td>
<td class="num">(209,068)<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 gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(2,056)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(2,056)<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">(137)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(137)<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">$ 2<span></span>
</td>
<td class="nump">26,203<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">26,205<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_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">1,684<span></span>
</td>
<td class="text">&#160;<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">62,068<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">62,068<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_StockholdersEquity', window );">Balance at Jun. 30, 2024</a></td>
<td class="nump">$ 146<span></span>
</td>
<td class="nump">2,303,369<span></span>
</td>
<td class="num">(34,838)<span></span>
</td>
<td class="num">(2,004,979)<span></span>
</td>
<td class="nump">263,698<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, 2024</a></td>
<td class="nump">146,025<span></span>
</td>
<td class="text">&#160;<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_StockholdersEquity', window );">Balance at Mar. 31, 2024</a></td>
<td class="nump">$ 146<span></span>
</td>
<td class="nump">2,270,047<span></span>
</td>
<td class="num">(34,964)<span></span>
</td>
<td class="num">(1,938,714)<span></span>
</td>
<td class="nump">296,515<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 Mar. 31, 2024</a></td>
<td class="nump">145,845<span></span>
</td>
<td class="text">&#160;<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">(66,265)<span></span>
</td>
<td class="num">(66,265)<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 gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">150<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">150<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">(24)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(24)<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">2,594<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">2,594<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">180<span></span>
</td>
<td class="text">&#160;<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">30,728<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">30,728<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_StockholdersEquity', window );">Balance at Jun. 30, 2024</a></td>
<td class="nump">$ 146<span></span>
</td>
<td class="nump">$ 2,303,369<span></span>
</td>
<td class="num">$ (34,838)<span></span>
</td>
<td class="num">$ (2,004,979)<span></span>
</td>
<td class="nump">$ 263,698<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, 2024</a></td>
<td class="nump">146,025<span></span>
</td>
<td class="text">&#160;<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;">
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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 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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 35<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480483/718-10-35-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 13<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481089/718-20-55-13<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481089/718-20-55-12<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><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>
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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>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</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_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>
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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_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 adjustment, of gain (loss) in value of unsold investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), attributable to 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> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 19<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481231/810-10-45-19<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 20<br> -SubTopic 10<br> -Topic 810<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481231/810-10-45-20<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(3)<br> -SubTopic 10<br> -Topic 810<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481203/810-10-50-1A<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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</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://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 220<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-10A<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-11<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-10A<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-10A<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481839/830-10-45-9<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 35<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482014/830-20-35-3<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481694/830-30-45-12<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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481112/505-10-50-2<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;">us-gaap_SharesIssued</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>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_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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481112/505-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480008/505-10-S99-1<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;">us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation</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:sharesItemType</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>
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<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>
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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>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 );">- Definition</a><div><p>Amount of equity (deficit) attributable to parent. Excludes temporary equity and equity 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://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(31))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 5: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 946<br> -SubTopic 830<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479168/946-830-55-12<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(19))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.6-05(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479170/946-210-S99-2<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(7))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479134/946-220-S99-3<br><br>Reference 11: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 12: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 323<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481687/323-10-50-3<br><br>Reference 13: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-28<br><br>Reference 14: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 310<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 4.E)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480418/310-10-S99-2<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;">us-gaap_StockholdersEquity</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>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492880314928">
<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">3 Months Ended</th>
<th class="th" colspan="2">6 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</div></th>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</div></th>
<th class="th"><div>Dec. 31, 2023</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>
<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="num">$ (66,265)<span></span>
</td>
<td class="num">$ (85,290)<span></span>
</td>
<td class="num">$ (209,068)<span></span>
</td>
<td class="num">$ (209,613)<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_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>
<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_Depreciation', window );">Depreciation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,013<span></span>
</td>
<td class="nump">5,225<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_OperatingLeaseRightOfUseAssetAmortizationExpense', window );">Amortization of right-of-use operating lease assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4,957<span></span>
</td>
<td class="nump">4,826<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_AmortizationOfIntangibleAssets', window );">Amortization of other assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,260<span></span>
</td>
<td class="nump">1,244<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_AccretionAmortizationOfDiscountsAndPremiumsInvestments', window );">Amortization of discount on investments, net</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(19,143)<span></span>
</td>
<td class="num">(12,481)<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_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3,338<span></span>
</td>
<td class="nump">2,966<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_RoyaltyPayments', window );">Non-cash royalty revenue related to sale of royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(16,236)<span></span>
</td>
<td class="num">(12,562)<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_InterestExpenseRelatedToSaleOfFutureRoyalties', window );">Non-cash interest related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">35,949<span></span>
</td>
<td class="nump">32,915<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_ShareBasedCompensation', window );">Stock-based compensation expense</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">62,068<span></span>
</td>
<td class="nump">53,510<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_RealizedInvestmentGainsLosses', window );">Loss (gain) on investments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,201<span></span>
</td>
<td class="num">(301)<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 );">Gain on early retirement of debt</a></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">(11,292)<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_ImpairmentOfIntangibleAssetsFinitelived', window );">Non-cash losses related to other assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">389<span></span>
</td>
<td class="nump">775<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_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>
<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_IncreaseDecreaseInContractWithCustomerAsset', window );">Contracts receivable</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,519<span></span>
</td>
<td class="num">(2,254)<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_IncreaseDecreaseInInventories', window );">Inventories</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(298)<span></span>
</td>
<td class="num">(3,505)<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_IncreaseDecreaseInOtherOperatingAssets', window );">Other current and long-term assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(9,381)<span></span>
</td>
<td class="num">(19,696)<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_IncreaseDecreaseInAccruedIncomeTaxesPayable', window );">Income taxes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(1,867)<span></span>
</td>
<td class="nump">18,483<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_IncreaseDecreaseInAccountsPayable', window );">Accounts payable</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(17,064)<span></span>
</td>
<td class="nump">5,517<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_IncreaseDecreaseInOtherEmployeeRelatedLiabilities', window );">Accrued compensation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(32,709)<span></span>
</td>
<td class="num">(19,856)<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_IncreaseDecreaseInOtherCurrentLiabilities', window );">Accrued liabilities and other current liabilities</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(39,201)<span></span>
</td>
<td class="num">(37,562)<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_IncreaseDecreaseInContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(109,545)<span></span>
</td>
<td class="num">(27,695)<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_NetCashProvidedByUsedInOperatingActivities', window );">Net cash used in operating activities</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(269,818)<span></span>
</td>
<td class="num">(231,356)<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_NetCashProvidedByUsedInInvestingActivitiesAbstract', window );"><strong>Investing activities:</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_PaymentsToAcquireAvailableForSaleSecuritiesDebt', window );">Purchases of short-term investments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(803,867)<span></span>
</td>
<td class="num">(932,362)<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_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities', window );">Proceeds from sale of short-term investments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">968,413<span></span>
</td>
<td class="nump">701,034<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_PaymentsToAcquirePropertyPlantAndEquipment', window );">Purchases of property, plant and equipment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(10,727)<span></span>
</td>
<td class="num">(22,483)<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_PaymentsToAcquireIntangibleAssets', window );">Acquisition of licenses and other assets, net</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(15,264)<span></span>
</td>
<td class="num">(2,314)<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_NetCashProvidedByUsedInInvestingActivities', window );">Net cash provided by (used in) investing activities</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">138,555<span></span>
</td>
<td class="num">(256,125)<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_NetCashProvidedByUsedInFinancingActivitiesAbstract', window );"><strong>Financing activities:</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_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions', window );">Proceeds from equity, net</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">26,205<span></span>
</td>
<td class="nump">4,950<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_ProceedsFromConvertibleDebt', window );">Proceeds from issuance of 1.75 percent convertible senior notes</a></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">575,000<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_PaymentsOfDebtIssuanceCosts', window );">1.75 percent convertible senior notes issuance costs</a></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">(13,658)<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 $434.1 million principal amount of 0.125 percent convertible senior notes</a></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">(420,158)<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_ProceedsFromSaleOfFutureRoyalties', window );">Proceeds from sale of future royalties</a></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">500,000<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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Payments of transaction costs related to sale of future royalties</a></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">(10,434)<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 );">Principal payments on mortgage debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(78)<span></span>
</td>
<td class="num">(75)<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_NetCashProvidedByUsedInFinancingActivities', window );">Net cash provided by financing activities</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">26,127<span></span>
</td>
<td class="nump">635,625<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_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations', window );">Effects of exchange rates on cash</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(137)<span></span>
</td>
<td class="nump">174<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_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect', window );">Net increase (decrease) in cash and cash equivalents</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(105,273)<span></span>
</td>
<td class="nump">148,318<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_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at beginning of period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">399,266<span></span>
</td>
<td class="nump">276,472<span></span>
</td>
<td class="nump">$ 276,472<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 end of period</a></td>
<td class="nump">$ 293,993<span></span>
</td>
<td class="nump">$ 424,790<span></span>
</td>
<td class="nump">293,993<span></span>
</td>
<td class="nump">424,790<span></span>
</td>
<td class="nump">$ 399,266<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_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>
<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_InterestPaidNet', window );">Interest paid</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,569<span></span>
</td>
<td class="nump">529<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_IncomeTaxesPaid', window );">Income taxes paid</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,992<span></span>
</td>
<td class="nump">510<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_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>
<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_NonCashCapitalAndPatentExpenditures', window );">Amounts accrued for capital and patent expenditures</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,453<span></span>
</td>
<td class="nump">$ 251<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_InterestExpenseRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 interest expense using the effective interest rate method related to the sale of future royalties.</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_InterestExpenseRelatedToSaleOfFutureRoyalties</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_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_ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 for transaction costs in connection with a monetization transaction of future SPINRAZA and pelacarsen royalties the Company is entitled to under collaboration and licensing agreements.</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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties</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_ProceedsFromSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 future royalties under a royalty purchase 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_ProceedsFromSaleOfFutureRoyalties</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_ions_RoyaltyPayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 royalty payments made during the period under a royalty purchase 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_RoyaltyPayments</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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1F<br> -Subparagraph (b)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1F<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-3<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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 350<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482640/350-30-55-40<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 350<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482665/350-30-50-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 350<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482686/350-30-45-2<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;">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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482913/230-10-50-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-24<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-4<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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-24<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -SubTopic 230<br> -Topic 830<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477401/830-230-45-1<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;">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>
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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_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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482099/360-10-50-1<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;">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> -Topic 830<br> -SubTopic 230<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477401/830-230-45-1<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;">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_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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481303/470-50-40-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481303/470-50-40-4<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/2003/role/disclosureRef<br> -Topic 350<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482686/350-30-45-2<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 350<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482665/350-30-50-3<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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>Amount, before refund, of cash paid to foreign, federal, state, and local jurisdictions as income tax.</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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482913/230-10-50-2A<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 23<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-23<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-22<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-25<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482913/230-10-50-2<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;">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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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/2003/role/disclosureRef<br> -Topic 912<br> -SubTopic 310<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478345/912-310-45-11<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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>
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<td><strong> Balance Type:</strong></td>
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<tr>
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<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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 17<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-17<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (e)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-25<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482913/230-10-50-2<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>
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<td><strong> Balance Type:</strong></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>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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-24<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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
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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 );">- 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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-24<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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<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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
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<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<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 );">- 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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-24<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-25<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>
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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_NetCashProvidedByUsedInOperatingActivitiesAbstract</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>
<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_us-gaap_NetIncomeLoss">
<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>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
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http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482689/260-10-45-60B<br><br>Reference 33: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 205<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483499/205-20-50-7<br><br>Reference 34: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<br><br>Reference 35: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-1A<br><br>Reference 36: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-1B<br><br>Reference 37: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478524/942-220-S99-1<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;">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>
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</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 periodic reduction over lease term of carrying amount of 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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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_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> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (e)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481830/320-10-45-11<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-13<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-11<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_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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-13<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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-13<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> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-14<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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-14<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 718<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2A<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_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/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481830/320-10-45-11<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-11<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-12<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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(3)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<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;">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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<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>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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of noncash expense for 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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-28<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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<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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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492878521376">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical)<br> $ in Millions</strong></div></th>
<th class="th">
<div>Jun. 30, 2024 </div>
<div>USD ($)</div>
</th>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="nump">1.75%<span></span>
</td>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract', window );"><strong>Financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentRepurchasedFaceAmount', window );">Principal amount repurchased</a></td>
<td class="nump">$ 434.1<span></span>
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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://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<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><strong> Name:</strong></td>
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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>
<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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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882598432">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Basis of Presentation<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
</tr>
<tr><th class="th"><div>Jun. 30, 2024</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_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock', window );">Organization and Basis of Presentation</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.&#160; Organization and 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; font-weight: bold;">Organization and Business Activity</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 incorporated in California on January 10, 1989. In conjunction with our initial public offering, we reorganized as a Delaware
    corporation in April 1991. We are a leader in the discovery and development of RNA-targeted therapeutics.</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;">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 six months ended&#160;June 30, 2024 and 2023 on the same basis as the audited financial statements for the year ended December 31, 2023. 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, 2023 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>

<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_d751d8638e404708bbf18fb6bb90a9f5">single</span>
    segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a <span style="-sec-ix-hidden:Fact_baf534ae803246ddb035eb980683637d">single</span>
    operating segment.</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;">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 United States, or </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>
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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 organization, consolidation and basis of presentation of financial statements disclosure.</p></div>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492979190512">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies<br></strong></div></th>
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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="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our significant accounting policies have not changed substantially from those included in our Annual Report on Form 10-K for the year
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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;">Recently Issued Accounting Standards</div>

<div><br/>
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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 do not expect any recently issued accounting standards to have a material impact to our financial results.</div>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Supplemental Financial Data<br></strong></div></th>
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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 inventory consisted of the following (in thousands):</div>

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        </td>

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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; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

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    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF; white-space: nowrap;" 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>
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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">
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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">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
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        </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; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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; white-space: nowrap;" 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; 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">
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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;">22,794</div>
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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 style="vertical-align: bottom; width: 76%; white-space: nowrap;" valign="bottom">
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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>

    <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;">3,614</div>
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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>

    <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;">5,477</div>
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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 style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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        </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;">486</div>
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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; 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;">154</div>
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    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventories</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">
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        </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;">28,723</div>
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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>

    <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">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
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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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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>

<div><br/>
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<div><br/>
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    <td colspan="1" style="text-align: left; 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 style="vertical-align: bottom; width: 76%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="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%; border-bottom: #000000 solid 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">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 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">&#160;</td>

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    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</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; 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;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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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">
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        </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">
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        </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">
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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;">4,907</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">
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    <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: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other commercial revenue:</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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA revenue, net</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;">8,192</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;">10,655</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;">16,820</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;">17,133</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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</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;">3,320</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;">6,230</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;">14,704</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;">17,273</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; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total other commercial revenue</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;">11,512</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;">16,885</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;">31,524</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;">34,406</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: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</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;">72,036</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;">77,897</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;">131,629</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;">145,664</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development 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>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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; 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">&#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; 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">&#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; 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">&#160;</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; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaborative agreement revenue</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;">141,524</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;">91,013</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;">190,870</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">&#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;">129,347</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; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA joint development revenue</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;">11,690</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;">19,501</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;">22,249</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;">43,924</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: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research and development revenue</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;">153,214</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;">110,514</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;">213,119</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;">173,271</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>

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    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: 54pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</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;">225,250</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;">188,411</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;">344,748</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;">318,935</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 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-weight: bold;"><span style="text-decoration: underline;">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;">The following are sources of revenue and when we typically recognize 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: SPINRAZA royalties and WAINUA 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;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. In 2024, we began earning royalties from
    WAINUA 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; 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;">We earn commercial revenue from TEGSEDI and WAYLIVRA sales under our distribution agreements with Sobi. In addition, we receive royalties
    from PTC Therapeutics International Limited, or PTC, for TEGSEDI&#160; and WAYLIVRA 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; font-style: italic;">Commercial Revenue: 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;">&#160;We also recognize as commercial revenue sales milestone payments and royalties we earn under our partnerships. For example, we earn
    royalty revenue on net sales of QALSODY, which is included in 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; font-style: italic;">Research and development revenue under collaboration 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Upfront payments:</span></span> 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. If part or all of the upfront payment is a license fee, we recognize as revenue the portion related to the license when we deliver the license to our partner because our partner has full use of
    the license and we do not have any additional performance obligations related to the license after delivery.</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; font-style: italic;"><span style="text-decoration: underline;">Milestone payments:</span></span> We
    include variable 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 R&amp;D 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, when we
    achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&amp;D services performance obligation and
    recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone payment to 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;">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.</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; font-style: italic;"><span style="text-decoration: underline;">License fees:</span></span> We 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 because our partner has full use of the license and we do not have any additional performance obligations
    related to the license after delivery.</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;">WAINUA (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 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize WAINUA for the
    treatment of transthyretin amyloidosis, or ATTR. We jointly developed and are commercializing WAINUA<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>with AstraZeneca in the U.S. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for the treatment of adults with polyneuropathy caused by hereditary ATTR, or ATTRv-PN.</span> We initially granted AstraZeneca exclusive rights to commercialize WAINUA outside the U.S., except for
    certain Latin American countries. In 2023, we expanded those rights to include 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 WAINUA 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 Accounting Standards Codification, or ASC, Topic 606, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span>, or ASC 606, for the license we granted to AstraZeneca and as a result we had one performance obligation. 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 Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or 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 currently 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 WAINUA 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 selling,
    general and administrative, or SG&amp;A, expense and R&amp;D expense, respectively.</div>
<span></span>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882063952">
<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">6 Months Ended</th>
</tr>
<tr><th class="th"><div>Jun. 30, 2024</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_ions_CollaborativeArrangementsAndLicensingAgreementsAbstract', window );"><strong>Collaborative Arrangements and Licensing Agreements [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_CollaborativeArrangementDisclosureTextBlock', window );">Collaborative Arrangements and Licensing Agreements</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#160; Collaborative Arrangements and Licensing Agreements</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;">Below, we have included our AstraZeneca, Biogen, Otsuka and
      Roche collaborations, which are the collaborations with substantive changes during 2024 from those included in Part IV, Item 15, Note 4, </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;">, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2023.</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;">AstraZeneca</div>

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  </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 have </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> collaborations with AstraZeneca, </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> focused on the joint development and commercialization of WAINUA and </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> focused on the treatment of cardiovascular, renal and metabolic diseases. From inception through </span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received more than $</span>920<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million from these collaborations.</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;">Over the term of our WAINUA collaboration, we are eligible to receive up to $3.6 billion, which is comprised of a $200 million upfront payment, up to $485 million in development and approval milestone payments and up to $2.9 billion in sales milestone payments. The agreement includes territory-specific development, commercial and medical affairs cost-sharing provisions. In addition, we are eligible to receive up
    to mid-20 percent royalties for sales in the U.S. and tiered royalties up to the high teens for sales outside the U.S.</div>

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  </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 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with ATTRv-PN. As a result, we began earning
    royalties from WAINUA sales, which we recognize as commercial revenue in our condensed consolidated statements of operations. We will achieve the next payment of up to $30 million upon regulatory approval of WAINUA for ATTRv-PN in the European Union, or EU, under this collaboration.</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;">During the three and six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentage amounts):</div>

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  </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">

        </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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">2024</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;">2023</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;">2024</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;">2023</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;">Revenue from our relationship with AstraZeneca</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;">15,960</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;">59,501</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;">27,645</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;">83,926</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;">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>

    <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</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;">32</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;">8</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;">26</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>


</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;">Our condensed consolidated balance sheet at June 30, 2024 included deferred contract revenue of $1.9 million from our relationship
    with AstraZeneca. We did not have any deferred contract revenue from our relationship with AstraZeneca at December 31, 2023.</div>

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  </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. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. QALSODY, our medicine to treat patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS,
    received accelerated approval from the U.S. Food and Drug Administration, or FDA, in April 2023 and marketing authorization under exceptional circumstances from the European Medicines Agency, or EMA, in May 2024. In addition, we and Biogen are
    currently developing numerous other investigational medicines to treat neurodegenerative diseases, including medicines in development to treat people with amyotrophic lateral sclerosis, or ALS, SMA, Alzheimer&#8217;s disease, or AD, and Parkinson&#8217;s disease,
    or PD. 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 June 30, 2024, we have received more than $3.9 billion in payments from our Biogen
    collaborations, including payments to purchase our stock.</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 2013 strategic neurology collaboration, we earned a $20 million milestone payment from Biogen when the EMA approved Biogen&#8217;s Marketing Authorization Application, or MAA, filing of QALSODY in the second quarter of 2024. We recognized this milestone
    payment as R&amp;D revenue in full in the second quarter of 2024 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next milestone payment for QALSODY of $10 million if the Ministry of Health, Labour and Welfare of Japan approves Biogen&#8217;s Japanese New Drug Application filing of QALSODY.</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 second quarter of 2024, Biogen's option to license ION582, an investigational antisense medicine for the potential treatment of
    Angelman Syndrome, expired unexercised. As a result, we recognized $30 million of R&amp;D revenue from previously deferred milestone payments
    related to the ION582 study because we did not have any remaining performance obligations. We will achieve the next milestone payment of $25
    million if Biogen advances IONIS-MAPT<sub>Rx</sub> into Phase 3 development under our 2012 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;">During the three and six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Biogen (in thousands, 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">

        </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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">2024</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;">2023</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;">2024</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;">2023</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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Biogen</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;">138,159</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;">97,402</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;">197,395</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;">167,903</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: -8.9pt; 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>

    <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;">61</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;">52</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;">57</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;">53</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>


</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;">Our condensed consolidated balance sheets at June 30, 2024 and December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>included deferred contract revenue of $241.8 million and $307.4 million, respectively, from 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; font-style: italic; font-weight: bold;">Otsuka</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 2023, we entered into an agreement with Otsuka
      Pharmaceutical Co., Ltd., or Otsuka, to commercialize donidalorsen in Europe. In the second quarter of 2024, we expanded the agreement to include commercialization rights for donidalorsen in the Asia-Pacific region in addition to Europe. As a result,
      we received a $</span>20<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment from Otsuka.
      Under the amended agreement, we are eligible to receive up to $</span>290<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, which is comprised of $</span>85<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in
      upfront payments, up to $</span>65<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestone
      payments and up to $</span>140<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in sales milestone payments
      over the term of the collaboration. In addition, we are eligible to receive tiered royalties up to </span>30 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales. We are responsible for completing the ongoing development of donidalorsen. We retained the rights to commercialize donidalorsen in the U.S. and in the rest of the world, assuming
      regulatory approvals. </span>From inception through June 30, 2024, we have received $85 million in payments from Otsuka.</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 identified two performance
    obligations under our amended agreement for the Asia-Pacific region, comprised of our license of donidalorsen to Otsuka and R&amp;D services for donidalorsen. We allocated the transaction price of $20 million based on the estimated stand-alone selling price of each performance obligation as follows:</div>

<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: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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;">$17.5 million for the license of donidalorsen; and</div>
        </td>

  </tr>


</table>

<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: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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;">$2.5 million for the R&amp;D services for donidalorsen.</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;">In the second quarter of 2024, we recognized $17.5
    million as revenue in full because Otsuka had full use of the license without any continuing involvement from us. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our
    performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our R&amp;D services performance obligation in March 2026. We will achieve the next payment of $15 million if the EMA accepts a MAA filing for donidalorsen in the EU under this 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;">During the three and six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Otsuka (in thousands, 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%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">2024</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;">2023</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;">2024</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;">2023</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;">Revenue from our relationship with Otsuka</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;">18,905</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;">&#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">
          <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;">19,691</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;">&#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>

  </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>

    <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">
          <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</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;">6</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</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>


</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;">Our condensed consolidated balance sheets at June 30, 2024 and December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>included deferred contract revenue of $8.8 million and $8.5 million, respectively, from our relationship with Otsuka.</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 three collaborations
    with Hoffmann-La Roche Inc. and F. Hoffmann-La Roche Ltd, collectively Roche: one to <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">develop </span>treatments for Huntington&#8217;s disease, or HD, 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 immunoglobulin A, or IgA, nephropathy, or IgAN, and one to develop RNA-targeted programs for AD and HD. From inception through June 30, 2024, we have received more than $345 million in payments 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In July 2024, Roche discontinued development</span> of
    IONIS-FB-L<sub>Rx</sub> for the treatment of geographic atrophy, or GA, following the completion of the Phase 2 study, which showed a favorable safety profile and target engagement, but insufficient efficacy to advance into Phase 3 development.</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;">Over the term of the IONIS-FB-L<sub>Rx</sub> collaboration for the treatment of IgAN, we are eligible to receive up to $430 million, which is comprised of a $35 million
    license fee, up to $25 million in development milestone payments, up to $90 million in regulatory milestone payments and up to $280 million in sales milestone
    payments. We will achieve the next payment of $23.5 million if Roche advances IONIS-FB-L<sub>Rx</sub> for the treatment of IgAN under this
    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;">During the three and six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Roche (in thousands, 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%;">


  <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="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;">June 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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">2024</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;">2023</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;">2024</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;">2023</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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Roche</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;">11,089</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;">5,754</div>
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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>

    <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;">22,595</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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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,121</div>
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          <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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</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>

    <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</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>
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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;">7</div>
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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>
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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;">3</div>
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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/>
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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 condensed consolidated balance sheets at June 30, 2024 and December 31, 2023 included deferred contract revenue of $15.0 million and $36.7 million, respectively,
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for collaborative arrangements in which the entity is a participant, including a) information about the nature and purpose of such arrangements; b) its rights and obligations thereunder; c) the accounting policy for collaborative arrangements; and d) the income statement classification and amounts attributable to transactions arising from the collaborative arrangement between participants.</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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 808<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479402/808-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 808<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479402/808-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Topic 808<br> -Publisher FASB<br> -URI https://asc.fasb.org/808/tableOfContent<br></p></div>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882569520">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basic and Diluted Net Loss Per Share<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
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<tr><th class="th"><div>Jun. 30, 2024</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;">6. Basic and Diluted Net Loss Per Share</div>

<div><br/>
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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;">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 six months ended&#160;June 30, 2024 and 2023 by dividing our net loss by our weighted-average number of common shares outstanding during the 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-weight: bold;">Diluted net loss per share</div>

<div><br/>
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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 three and six months ended&#160;June 30, 2024 and 2023, 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/>
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    <td style="width: 18pt; vertical-align: top; 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;">1.75 percent convertible senior notes, or 1.75% Notes;</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;">0 percent convertible senior notes, or 0% Notes;</div>
        </td>

  </tr>


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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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>
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    <td style="width: 18pt; vertical-align: top; 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>
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  </tr>


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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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>


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
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        </td>

  </tr>


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>

<div><br/>
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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 June 30, 2024
    and 2023, 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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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for earnings per share.</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> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org/260/tableOfContent<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-3<br></p></div>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492880022640">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
</tr>
<tr><th class="th"><div>Jun. 30, 2024</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_InvestmentsAbstract', window );"><strong>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_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;">7.&#160; 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;">The following table summarizes the contract maturity of the available-for-sale securities we held as of June 30, 2024:</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: 9pt; 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;">75</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: 9pt; 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;">21</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: 9pt; 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;">4</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: 9pt; 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>

  </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;">As illustrated above, at June 30, 2024,
    96 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.</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 debt 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, 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 June 30, 2024, we had an
    equity ownership interest of less than 20 percent in seven 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: justify; 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><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">

        </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; 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; font-weight: bold;"><span style="text-indent: 0pt;">June 30, 2024</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 debt 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;">552,837</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;">36</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;">(1,569</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;">551,304</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;">121,781</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</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;">(310</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;">121,476</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;">650,997</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;">12</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;">(1,105</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;">649,904</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;">18,083</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;">14</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;">(42</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;">18,055</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 debt 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;">1,343,698</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;">67</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;">(3,026</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;">1,340,739</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;">218,639</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;">191</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;">(874</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;">217,956</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 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;">115,349</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;">72</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;">(317</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;">115,104</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 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;">127,240</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;">(1,135</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;">126,117</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;">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; 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;">1,668</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;">(8</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;">1,660</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 debt securities with a maturity of more than one year</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;">462,896</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;">275</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;">(2,334</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;">460,837</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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale 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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,806,594</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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">342</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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,360</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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,801,576</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;"><span style="text-decoration: underline;">Equity securities:</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">&#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; 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">&#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; 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">&#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; 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">&#160;</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;">Publicly traded equity securities included in other current assets (2)</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;">11,897</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;">334</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;">(5,377</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;">6,854</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;">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;" 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;">23,115</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;">25,001</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;">(7,093</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;">41,023</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 equity 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;">35,012</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;">25,335</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;">(12,470</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;">47,877</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: 4px;" 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 debt and equity securities</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;">1,841,606</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;">25,677</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;">(17,830</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 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; 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;">1,849,453</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>

<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">

        </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; 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; font-weight: bold;"><span style="text-indent: 0pt;">December 31, 2023</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 debt 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;">559,967</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;">157</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;">(2,625</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;">557,499</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;">224,711</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;">64</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;">(611</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;">224,164</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;">513,784</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;">152</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;">(1,889</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;">512,047</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;">17,757</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;">42</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;">(113</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;">17,686</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 debt 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;">1,316,219</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;">415</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;">(5,238</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;">1,311,396</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;">243,151</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;">1,270</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;">(692</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;">243,729</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 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;">110,138</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;">547</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;">(21</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;">110,664</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 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;">294,873</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;">1,239</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;">(480</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;">295,632</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;">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; 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;">3,466</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</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;">(4</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;">3,469</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 debt securities with a maturity of more than one year</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;">651,628</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <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;">3,063</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;">(1,197</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;">653,494</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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale 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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,967,847</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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,478</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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,435</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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,964,890</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;"><span style="text-decoration: underline;">Equity securities:</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">&#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; 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">&#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; 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">&#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; 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">&#160;</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;">Publicly traded equity securities included in other current assets (2)</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;">11,897</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;">236</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;">(5,832</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;">6,301</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;">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;" 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;">23,115</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;">25,001</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;">(5,125</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;">42,991</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 equity 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;">35,012</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;">25,237</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;">(10,957</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;">49,292</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: 4px;" 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 debt and equity securities</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;">2,002,859</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;">28,715</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;">(17,392</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 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; 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;">2,014,182</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>

<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; 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 sheets.</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; 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 publicly traded equity securities are
            included in other current assets. We recognize publicly traded equity securities at fair value. In the six months ended&#160;June 30, 2024, we recorded a $0.6
            million net unrealized gain in our condensed consolidated statements of operations related to changes 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; 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 privately held equity securities are included in deposits and other assets. We recognize our privately held 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, which are Level 3 inputs<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In the </span>six months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recorded a loss of $</span>2.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in our condensed consolidated statements of operations related to changes in the
              fair value of our investments in privately held companies.</span></div>
        </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;">The following is a summary of our investments we consider to be temporarily impaired at June 30, 2024 (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;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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; white-space: nowrap;" 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>
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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>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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; white-space: nowrap;" 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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" 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; white-space: nowrap;" 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>
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    <td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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;">440</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;">517,394</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;">(1,155</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;">142,390</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;">(1,288</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;">659,784</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;">(2,443</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%;" 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;">108</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;">173,618</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;">(482</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;">25,892</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;">(145</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;">199,510</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;">(627</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;" 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;">71</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;">561,363</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;">(862</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;">154,006</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;">(1,378</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;">715,369</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;">(2,240</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%; 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;">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;">8,449</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</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;">9,319</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;">(27</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;">17,768</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;">(50</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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; 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 temporarily impaired 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">&#160;</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;">664</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;">1,260,824</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;">(2,522</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;">331,607</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;">(2,838</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;">1,592,431</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;">(5,360</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>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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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 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 intend to hold these securities
    to maturity and anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</div>
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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">6 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;">8.&#160; Fair Value Measurements</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 tables present the major security types we held at June 30, 2024 and December 31, 2023 that we regularly measure and carry at fair
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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </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; white-space: nowrap;" 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;">June 30, 2024</div>
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    <td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</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>

  </tr>

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    <td style="vertical-align: bottom; width: 64%; 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;">Cash equivalents (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;">212,489</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;">212,489</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;">&#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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" 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 (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">&#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;">769,260</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;">769,260</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: 64%; 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;">236,580</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;">236,580</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: 64%;" 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 (3)</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;">776,021</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;">776,021</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: 64%; 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 (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;">19,715</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;">19,715</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: 64%; padding-bottom: 2px;" 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 (4)</div>
          </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;">6,854</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;">6,854</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;">&#8212;</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: 64%; padding-bottom: 4px; background-color: #CCEEFF;" 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; 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;">2,020,919</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;">995,364</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;">1,025,555</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="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">

        </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; white-space: nowrap;" 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, 2023</div>
        </td>

    <td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</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: 64%; 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;">Cash equivalents (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;">185,424</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">
          <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;">185,424</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">
          <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;">&#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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" 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 (5)</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;">801,228</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;">801,228</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: 64%; 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;">334,828</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;">334,828</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: 64%;" 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 (3)</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;">807,679</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;">807,679</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: 64%; 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 (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;">21,155</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;">21,155</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: 64%; padding-bottom: 2px;" 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 (4)</div>
          </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;">6,301</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;">6,301</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;">&#8212;</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: 64%; padding-bottom: 4px; background-color: #CCEEFF;" 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; 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;">2,156,615</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;">999,404</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;">1,157,211</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>

<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 sheets:</div>

<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; 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.</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; 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;">$16.9 million was included in cash and cash equivalents, with the difference included in short-term investments.</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; 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>

<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; 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;">Included in other current assets.</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; 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;">$33.0 million was included in cash and cash equivalents, with the difference included in short-term investments.</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;">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 1.75% Notes, 0% Notes and 0.125% Notes had a fair
    value of $634.4 million, $649.6
    million and $43.4 million at June 30, 2024,
    respectively. Our 1.75% Notes, 0%
    Notes and 0.125% Notes had a fair value of $661.1
    million, $667.8 million and $42.4
    million at December 31, 2023, 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;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492879150016">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stock-based Compensation Expense<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
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<tr><th class="th"><div>Jun. 30, 2024</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;">9. 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;">The following table summarizes stock-based compensation expense for the three and six months ended&#160;June 30, 2024 and 2023 (in thousands):</div>

<div><br/>
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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 rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"></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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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">

        </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;">2024</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;">2023</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;">2024</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;">2023</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;">246</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;">118</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;">450</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;">237</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;">22,766</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;">19,249</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;">44,991</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;">38,816</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;">7,716</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;">7,194</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;">16,627</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;">14,457</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: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stock-based compensation expense</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;">30,728</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;">26,561</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;">62,068</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;">53,510</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 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 June 30, 2024, total
    unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $61.6 million, $96.7 million and $13.8 million, respectively. Our
    actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures, including any PRSUs that do not vest. 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 1.3 years, 1.6 years and 1.9 years, 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;">Refer to Part IV, Item 15, 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, 2023 for further details on how we determine the fair value of stock options granted, RSUs, PRSUs and stock purchase rights under the 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;">For the six months ended&#160;June 30, 2024 and 2023, we used the
    following weighted-average assumptions in our Black-Scholes calculations:</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;">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">

        </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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">2024</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;">2023</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;">4.1</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;">3.6</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;">43.9</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;">47.3</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;">6.3 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">

        </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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">2024</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;">2023</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;">5.3</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>

    <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;">5.2</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>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
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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>
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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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          <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>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38.4</div>
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          <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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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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          <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: 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>
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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; font-style: italic;">RSUs:</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 weighted-average grant date fair value of RSUs granted to employees for the six months ended&#160;June 30, 2024 and 2023 was $52.60 and $39.50 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;">PRSUs:</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 terms of the PRSUs we granted in 2024 and 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period
    based on our relative TSR as compared to a peer group of companies and as measured at the end of the 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
    to 200 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;">The weighted-average grant date fair value of PRSUs we granted to our executive officers for the six months ended&#160;June 30, 2024 and 2023 was $78.41 and $58.99 per share, respectively.</div>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492879149600">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
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<tr><th class="th"><div>Jun. 30, 2024</div></th></tr>
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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;">10.&#160; Income Taxes</div>

<div><br/>
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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 recorded income tax expense of $0.1
    million and $0.1 million for the three and six months ended&#160;June 30, 2024, respectively, compared to $7.8 million and $19.2 million for the same periods in 2023, respectively. The decrease in income tax expense relates primarily to the impact of the royalty purchase agreement with Royalty Pharma on income tax
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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 continue to maintain a full valuation allowance on all our net deferred tax assets.</div>
<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for income tax.</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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12C<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12C<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12B<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12B<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 270<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477891/740-270-50-1<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.5.Q1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479360/740-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 13<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480990/946-20-50-13<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org/740/tableOfContent<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 14<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-14<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 21<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-21<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 17<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-17<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 11.C)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479360/740-10-S99-2<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482603/740-30-50-2<br></p></div>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492879418784">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Liability Related to Sale of Future Royalties<br></strong></div></th>
<th class="th" colspan="1">6 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;">11. Liability Related to Sale of Future 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;">In January 2023, we entered into a royalty purchase agreement with Royalty Pharma to monetize a portion of our future SPINRAZA and
    pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. As a result, we received an upfront payment of $500
    million and we are eligible to receive up to $625 million in additional milestone payments. Under the terms of the agreement, Royalty Pharma will
    receive 25 percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to 45 percent of royalty payments in 2028, on up to $1.5 billion in annual sales. In
    addition, Royalty Pharma will receive 25 percent of any future royalty payments on pelacarsen, our medicine in development to treat patients
    with elevated lipoprotein(a)-driven cardiovascular disease. Royalty Pharma&#8217;s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $475 million or $550 million, depending on the timing and occurrence of FDA approval of
    pelacarsen.</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 upfront payment of $500
    million as a liability related to the sale of future royalties, net of transaction costs of $10.4 million, which we are amortizing over the
    estimated life of the arrangement using the effective interest rate method. We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We record royalty payments made to Royalty
    Pharma as a reduction of the liability.</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 the effective interest rate used to record interest expense under this agreement based on an estimate of future royalty
    payments to Royalty Pharma. As of June 30, 2024, the estimated effective interest rate under the agreement was 13.5 percent.</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 sets forth information on our liability related to sale of future royalties
    (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: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of future royalties in January 2023</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;">500,000</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;">Issuance costs related to sale of future royalties</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;">(10,434</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: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty payments to Royalty Pharma</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;">(44,628</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: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</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;">68,238</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; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties</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;">560</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: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net liability related to sale of future royalties as of December 31, 2023</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;">513,736</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; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty payments to Royalty Pharma</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;">(16,236</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: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</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;">35,949</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; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties</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;">305</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: top; width: 88%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net liability related to sale of future royalties as of June 30, 2024</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;">533,754</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 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;">There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of royalty
    payments from Biogen and Novartis, and result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the commercial sales of SPINRAZA, the regulatory approval and commercial sales of
    pelacarsen, competing products or other significant events. </div>
<span></span>
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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">6 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;">12. Convertible Debt</div>

<div><br/>
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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-style: italic;">1.75 Percent
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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;">In 2023, we completed a $575.0
    million offering of convertible senior notes and used $488.2 million of the net proceeds from the issuance of the 1.75% Notes to repurchase $504.4 million in
    principal of our 0.125% Notes. We expect to use the remaining net proceeds to settle the 0.125% Notes that remain outstanding and for general corporate and working capital purposes.</div>

<div><br/>
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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 June 30, 2024, we had the following
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<div><br/>
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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 style="vertical-align: top; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.75% 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;">575.0</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;">11.4</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">
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        </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_ac460e99cb6b43a8b64e987880ed0dd5">June 2028</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; width: 88%;" 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; 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;">1.75</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: top; width: 88%; 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; 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;">2.3</div>
        </td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </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;">53.73</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; 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;">Total shares of common stock subject to conversion</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;">10.7</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>


</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">0 Percent
    Convertible Senior Notes and Call Spread</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;">At June 30, 2024, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes outstanding (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%;">


  <tr>

    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">0% 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;">632.5</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;">5.5</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_edbb9fb31e834f86ad026d22e567df04">April 2026</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; width: 88%;" 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; 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</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: top; width: 88%; 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; 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>

  <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>

  <tr>

    <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>

  <tr>

    <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>


</table>

<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 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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes by increasing the effective conversion price on our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes. We increased our effective conversion price to $76.39
    with the same number of underlying shares as our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%&#160;</span>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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes, our note hedges are subject to adjustment. Additionally, our note hedges
    are exercisable upon conversion of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes. The note
    hedges will expire upon maturity of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes, or April
    2026. The note hedges and warrants are separate transactions and are not part of the terms of our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes. The holders of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> 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 sheets. Refer to Part IV, Item 15, 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, 2023 for our Call Spread accounting policy. 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;">As discussed above, in 2023, we repurchased $504.4
    million of our 0.125% 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;">At June 30, 2024, we had the following
    0.125% Notes outstanding with interest payable semi-annually (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%;">


  <tr>

    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" 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;">44.5</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;">0.1</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_9ad2e8b4fef74d3cab598aa38f5df4fd">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; width: 88%;" 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; 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;">0.125</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: top; width: 88%; 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; 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>

  <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;">83.28</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; 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>

  </tr>

  <tr>

    <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, excluding shares related to <span style="text-indent: 0pt;">0.125</span>% Notes that we have repurchased and are currently holding in 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;">0.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<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 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. As of </span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the note hedges and warrants remain outstanding.</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 sheets. 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;">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>1.75%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, 0%
      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></div>
<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for information about short-term and long-term debt arrangements, which includes amounts of borrowings under each line of credit, note payable, commercial paper issue, bonds indenture, debenture issue, own-share lending arrangements and any other contractual agreement to repay funds, and about the underlying arrangements, rationale for a classification as long-term, including repayment terms, interest rates, collateral provided, restrictions on use of assets and activities, whether or not in compliance with debt covenants, and other matters important to users of the financial statements, such as the effects of refinancing and noncompliance with debt covenants.</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> -Topic 470<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481544/470-10-50-6<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481544/470-10-50-6<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 405<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477092/405-40-50-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> 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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492879144928">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Legal Proceedings<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
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<tr><th class="th"><div>Jun. 30, 2024</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;">13. Legal Proceedings</div>

<div><br/>
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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;">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
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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;">There are no pending material legal proceedings to which we are a party or of which our property is the subject.</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>
<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> -Topic 450<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org/450/tableOfContent<br></p></div>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492876859296">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Insider Trading Arrangements<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<div>Jun. 30, 2024 </div>
<div>shares</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 quarter ended June 30, 2024, our Section 16 officers and directors adopted or terminated contracts, instructions or written plans for the purchase or sale of our securities as noted in the table below.</div>

<div><br/>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Contract, instruction or written plan intended to satisfy the affirmative defense conditions of Rule 10b5-1(c) under the Exchange Act.</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8220;Non-Rule 10b5-1 trading arrangement&#8221; as defined in item 408(c) of Regulation S-K under the Exchange Act.</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Action</div>
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    <td rowspan="2" style="width: 2.22%; vertical-align: bottom;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Trading Arrangement</div>
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    <td rowspan="2" style="width: 2.22%; vertical-align: bottom;">&#160;</td>

    <td rowspan="2" style="width: 10%; 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;">Total Shares to Be Sold</div>
        </td>

    <td rowspan="2" style="width: 2.22%; vertical-align: bottom;">&#160;</td>

    <td rowspan="2" style="width: 22.1%; 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;">Expiration Date</div>
        </td>

  </tr>

  <tr>

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    <td style="width: 9.24%; vertical-align: bottom; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Non-Rule 10b5-1**</div>
        </td>

  </tr>

  <tr>

    <td style="width: 15.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia</div>
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Chief Executive Officer</div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Termination</div>
        </td>

    <td style="width: 2.54%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10.16%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">June 26, 2024</div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 7.98%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">X</div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.24%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,442</div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 22.1%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_916e87d3015b45708cd1e86a514e8307">Upon the execution of all instructions provided in the plan</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 15.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Richard S. Geary</div>
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">EVP, Chief Development Officer</div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adoption</div>
        </td>

    <td style="width: 2.54%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10.16%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">April 8, 2024</div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 7.98%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">X</div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">241,732</div>
        </td>

    <td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 22.1%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The earlier to occur of (i) <span style="-sec-ix-hidden:Fact_d6467e3eb7f84e94a4d98fb98d8f059a">July 7, 2025</span>,
            and (ii) Upon the execution of all instructions provided in the plan</div>
        </td>

  </tr>


</table>
<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_ecd_IndividualAxis=ions_BrettMoniaMember', window );">Brett Monia [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_ecd_TradingArrByIndTable', window );"><strong>Trading Arrangements, by Individual</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_ecd_TrdArrIndName', window );">Name</a></td>
<td class="text">Brett P. Monia<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_ecd_TrdArrIndTitle', window );">Title</a></td>
<td class="text">Chief Executive Officer<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_ecd_Rule10b51ArrTrmntdFlag', window );">Rule 10b5-1 Arrangement Terminated</a></td>
<td class="text">true<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_ecd_NonRule10b51ArrTrmntdFlag', window );">Non-Rule 10b5-1 Arrangement Terminated</a></td>
<td class="text">false<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_ecd_TrdArrTerminationDate', window );">Termination Date</a></td>
<td class="text">June 26, 2024<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_ecd_TrdArrDuration', window );">Arrangement Duration</a></td>
<td class="text"> <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_ecd_TrdArrSecuritiesAggAvailAmt', window );">Aggregate Available</a></td>
<td class="nump">54,442<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_ecd_IndividualAxis=ions_RichardSGearyMember', window );">Richard S. Geary [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_ecd_TradingArrByIndTable', window );"><strong>Trading Arrangements, by Individual</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_ecd_TrdArrIndName', window );">Name</a></td>
<td class="text">Richard S. Geary<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_ecd_TrdArrIndTitle', window );">Title</a></td>
<td class="text">EVP, Chief Development Officer<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_ecd_Rule10b51ArrAdoptedFlag', window );">Rule 10b5-1 Arrangement Adopted</a></td>
<td class="text">true<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_ecd_NonRule10b51ArrAdoptedFlag', window );">Non-Rule 10b5-1 Arrangement Adopted</a></td>
<td class="text">false<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_ecd_TrdArrAdoptionDate', window );">Adoption Date</a></td>
<td class="text">April 8, 2024<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_ecd_TrdArrDuration', window );">Arrangement Duration</a></td>
<td class="text">456 days<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_ecd_TrdArrSecuritiesAggAvailAmt', window );">Aggregate Available</a></td>
<td class="nump">241,732<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ecd_MtrlTermsOfTrdArrTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 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;">ecd_MtrlTermsOfTrdArrTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ecd_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</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_ecd_NonRule10b51ArrAdoptedFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 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;">ecd_NonRule10b51ArrAdoptedFlag</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ecd_</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_ecd_NonRule10b51ArrTrmntdFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 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;">ecd_NonRule10b51ArrTrmntdFlag</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ecd_</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_ecd_Rule10b51ArrAdoptedFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 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;">ecd_Rule10b51ArrAdoptedFlag</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ecd_</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_ecd_Rule10b51ArrTrmntdFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 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;">ecd_Rule10b51ArrTrmntdFlag</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ecd_</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_ecd_TradingArrByIndTable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 2<br> -Subparagraph 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;">ecd_TradingArrByIndTable</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ecd_</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_ecd_TrdArrAdoptionDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 2<br> -Subparagraph 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;">ecd_TrdArrAdoptionDate</td>
</tr>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ecd_</td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<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>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 2<br> -Subparagraph C<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;">ecd_TrdArrDuration</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ecd_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<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_ecd_TrdArrIndName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 2<br> -Subparagraph 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;">ecd_TrdArrIndName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ecd_</td>
</tr>
<tr>
<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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<td><strong> Period Type:</strong></td>
<td>duration</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_ecd_TrdArrIndTitle">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 2<br> -Subparagraph 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;">ecd_TrdArrIndTitle</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ecd_</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>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882275424">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Basis of Presentation (Policies)<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
</tr>
<tr><th class="th"><div>Jun. 30, 2024</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_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Organization and Basis of Presentation [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_BasisOfAccountingPolicyPolicyTextBlock', window );">Basis of Presentation</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;">We prepared the unaudited interim condensed consolidated financial statements for the three and six months ended&#160;June 30, 2024 and 2023 on the same basis as the audited financial statements for the year ended December 31, 2023. 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, 2023 included in our Annual
    Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</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_ConsolidationPolicyTextBlock', window );">Consolidation</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;">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>
<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_SegmentReportingPolicyPolicyTextBlock', window );">Segment Information</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;">We operate as a <span style="-sec-ix-hidden:Fact_d751d8638e404708bbf18fb6bb90a9f5">single</span>
    segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a <span style="-sec-ix-hidden:Fact_baf534ae803246ddb035eb980683637d">single</span>
    operating segment.</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_UseOfEstimates', window );">Use of Estimates</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;">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 United States, or </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>
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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>
<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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483426/235-10-50-4<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481203/810-10-50-1<br></p></div>
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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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 47<br> -Subparagraph (bb)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-47<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 54<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-54<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 36<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-36<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 47<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482785/280-10-55-47<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (e)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-29<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 the use of estimates in the preparation of financial statements in conformity with generally accepted accounting principles.</p></div>
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<TEXT>
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<head>
<title></title>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492883371408">
<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">6 Months Ended</th>
</tr>
<tr><th class="th"><div>Jun. 30, 2024</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_AccountingPoliciesAbstract', window );"><strong>Significant Accounting Policies [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_NewAccountingPronouncementsPolicyPolicyTextBlock', window );">Recently Issued Accounting Standards</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;">Recently Issued 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;">We do not expect any recently issued accounting standards to have a material impact to our financial results.</div>
<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_AccountingPoliciesAbstract">
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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_AccountingPoliciesAbstract</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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<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 );">- 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>
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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;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492879149600">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basic and Diluted Net Loss Per Share (Policies)<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
</tr>
<tr><th class="th"><div>Jun. 30, 2024</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_EarningsPerShareAbstract', window );"><strong>Basic and Diluted Net Loss Per Share [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_EarningsPerSharePolicyTextBlock', window );">Basic and Diluted Net Loss Per Share</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;">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 six months ended&#160;June 30, 2024 and 2023 by dividing our net loss by our weighted-average number of common shares outstanding during the 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-weight: bold;">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 six months ended&#160;June 30, 2024 and 2023, 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>

<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: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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;">1.75 percent convertible senior notes, or 1.75% Notes;</div>
        </td>

  </tr>


</table>

<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: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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>


</table>

<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: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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>


</table>

<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: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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>

<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: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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>

<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: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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>

<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: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>

<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: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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>

  </tr>


</table>

<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: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; 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>

  </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;">Additionally, as of June 30, 2024
    and 2023, 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>
<span></span>
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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_EarningsPerShareAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for computing basic and diluted earnings or loss per share for each class of common stock and participating security. Addresses all significant policy factors, including any antidilutive items that have been excluded from the computation and takes into account stock dividends, splits and reverse splits that occur after the balance sheet date of the latest reporting period but before the issuance of the financial statements.</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> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-2<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;">us-gaap_EarningsPerSharePolicyTextBlock</td>
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<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;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882594192">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Supplemental Financial Data (Tables)<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
</tr>
<tr><th class="th"><div>Jun. 30, 2024</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_ions_SupplementalFinancialDataAbstract', window );"><strong>Supplemental Financial Data [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_ScheduleOfInventoryCurrentTableTextBlock', window );">Inventories</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;">Inventories</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; white-space: nowrap;" valign="bottom">

        </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; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30, 2024</div>
        </td>

    <td colspan="1" style="text-align: left; 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; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2023</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; 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;">Raw materials:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF; white-space: nowrap;" 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; 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;">22,211</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;">20,985</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; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,412</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; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,809</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; white-space: nowrap;" 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; 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;">24,623</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;">22,794</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%; white-space: nowrap;" 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%; 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;">3,614</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;">5,477</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; white-space: nowrap;" 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; 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;">486</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;">154</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; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventories</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">
          <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;">28,723</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; 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">
          <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;">28,425</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="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfAccruedLiabilitiesTableTextBlock', window );">Accrued Liabilities</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</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;">Our accrued liabilities 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; white-space: nowrap;" valign="bottom">

        </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; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30, 2024</div>
        </td>

    <td colspan="1" style="text-align: left; 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; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2023</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; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Clinical development expenses</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;">82,017</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;">105,967</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%; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In-licensing expenses</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;">10,603</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;">7,454</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: 76%; background-color: #CCEEFF; white-space: nowrap;" 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; 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;">4,583</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;">4,875</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; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other miscellaneous expenses</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,127</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; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">29,598</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 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; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">114,330</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; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 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; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">147,894</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>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_SupplementalFinancialDataAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_SupplementalFinancialDataAbstract</td>
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<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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<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_ScheduleOfAccruedLiabilitiesTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Tabular disclosure of the components of accrued liabilities.</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_ScheduleOfAccruedLiabilitiesTableTextBlock</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>dtr-types:textBlockItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</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_ScheduleOfInventoryCurrentTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Tabular disclosure of the carrying amount as of the balance sheet date of merchandise, goods, commodities, or supplies held for future sale or to be used in manufacturing, servicing or production 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(c))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483489/210-10-50-1<br></p></div>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882489408">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Revenues (Tables)<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
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<tr><th class="th"><div>Jun. 30, 2024</div></th></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>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 30,</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>

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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>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</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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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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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>

    <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>

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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>

    <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>

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  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
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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>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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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">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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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>
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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;">111,258</div>
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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>

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    <td style="vertical-align: bottom; width: 52%;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA royalties</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;">3,781</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;">4,907</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: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other commercial revenue:</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">
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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">
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        </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">
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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">
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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">
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        </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: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
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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">
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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;">6,230</div>
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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;">14,704</div>
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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;">17,273</div>
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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>

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    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom">
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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">
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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">
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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;">31,524</div>
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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">
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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 style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div>
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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">
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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;">77,897</div>
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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;">131,629</div>
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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;">145,664</div>
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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="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">&#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; 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">&#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; 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">&#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; 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">&#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>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
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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;">141,524</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;">91,013</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;">190,870</div>
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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;">129,347</div>
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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%; padding-bottom: 2px;" valign="bottom">
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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;">11,690</div>
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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;">19,501</div>
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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;">22,249</div>
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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;">43,924</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: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research and development revenue</div>
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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;">153,214</div>
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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;">110,514</div>
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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;">213,119</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;">173,271</div>
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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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom">
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        </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">
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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;">225,250</div>
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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>

    <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>
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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;">188,411</div>
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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>

    <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">
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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;">344,748</div>
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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>

    <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">
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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;">318,935</div>
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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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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492879663904">
<tr>
<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">6 Months Ended</th>
</tr>
<tr><th class="th"><div>Jun. 30, 2024</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_AstrazenecaCollaborationsMember', window );">AstraZeneca [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_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [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_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 six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with AstraZeneca (in thousands, 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%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">2024</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;">2023</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;">2024</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;">2023</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;">Revenue from our relationship with AstraZeneca</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;">15,960</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;">59,501</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;">27,645</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;">83,926</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;">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>

    <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</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;">32</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;">8</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;">26</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>


</table>
<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 [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 six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Biogen (in thousands, 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%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">2024</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;">2023</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;">2024</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;">2023</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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Biogen</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;">138,159</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;">97,402</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;">197,395</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;">167,903</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: -8.9pt; 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>

    <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;">61</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;">52</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;">57</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;">53</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>


</table>
<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_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [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_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [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_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 six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Otsuka (in thousands, 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%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">2024</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;">2023</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;">2024</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;">2023</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;">Revenue from our relationship with Otsuka</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;">18,905</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;">&#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">
          <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;">19,691</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;">&#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>

  </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>

    <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">
          <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</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;">6</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</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>


</table>
<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 [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 six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Roche (in thousands, 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%;">


  <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="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;">June 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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">2024</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;">2023</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;">2024</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;">2023</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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Roche</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;">11,089</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;">5,754</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;">22,595</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;">8,121</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;">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>

    <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</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;">3</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;">7</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;">3</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>


</table>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>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.</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_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems</td>
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<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><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_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock">
<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>Tabular disclosure of the nature of a concentration, a benchmark to which it is compared, and the percentage that the risk is to the benchmark.</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> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 21<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 16<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-16<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-21<br></p></div>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492880587120">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments (Tables)<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
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<tr><th class="th"><div>Jun. 30, 2024</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_InvestmentsAbstract', window );"><strong>Investments [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_InvestmentsClassifiedByContractualMaturityDateTableTextBlock', window );">Contract Maturity of Available-for-Sale Securities</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;">The following table summarizes the contract maturity of the available-for-sale securities we held as of June 30, 2024:</div>

<div><br/>
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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 style="vertical-align: bottom; width: 88%; 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-indent: 0pt;">One year</span>
            or less</div>
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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;">75</div>
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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>
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  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">one year</span>
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        </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;">21</div>
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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>

  </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: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">two years</span>
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        </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;">4</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>
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  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; 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>
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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>
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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_UnrealizedGainLossOnInvestmentsTableTextBlock', window );">Summary of 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 (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>

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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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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</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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          <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; 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; font-weight: bold;"><span style="text-indent: 0pt;">June 30, 2024</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 debt 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;">552,837</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;">36</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;">(1,569</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;">551,304</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;">121,781</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</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;">(310</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;">121,476</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;">650,997</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;">12</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;">(1,105</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;">649,904</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;">18,083</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;">14</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;">(42</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;">18,055</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 debt 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;">1,343,698</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;">67</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;">(3,026</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;">1,340,739</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;">218,639</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;">191</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;">(874</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;">217,956</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 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;">115,349</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;">72</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;">(317</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;">115,104</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 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;">127,240</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;">(1,135</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;">126,117</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;">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; 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;">1,668</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;">(8</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;">1,660</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 debt securities with a maturity of more than one year</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;">462,896</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;">275</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;">(2,334</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;">460,837</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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale 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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,806,594</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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">342</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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,360</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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,801,576</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;"><span style="text-decoration: underline;">Equity securities:</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">&#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; 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">&#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; 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">&#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; 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">&#160;</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;">Publicly traded equity securities included in other current assets (2)</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;">11,897</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;">334</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;">(5,377</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;">6,854</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;">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;" 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;">23,115</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;">25,001</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;">(7,093</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;">41,023</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 equity 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;">35,012</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;">25,335</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;">(12,470</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;">47,877</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: 4px;" 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 debt and equity securities</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;">1,841,606</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;">25,677</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;">(17,830</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 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; 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;">1,849,453</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>

<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">

        </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; 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; font-weight: bold;"><span style="text-indent: 0pt;">December 31, 2023</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 debt 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;">559,967</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;">157</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;">(2,625</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;">557,499</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;">224,711</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;">64</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;">(611</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;">224,164</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;">513,784</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;">152</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;">(1,889</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;">512,047</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;">17,757</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;">42</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;">(113</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;">17,686</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 debt 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;">1,316,219</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;">415</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;">(5,238</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;">1,311,396</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;">243,151</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;">1,270</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;">(692</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;">243,729</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 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;">110,138</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;">547</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;">(21</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;">110,664</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 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;">294,873</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;">1,239</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;">(480</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;">295,632</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;">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; 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;">3,466</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</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;">(4</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;">3,469</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 debt securities with a maturity of more than one year</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;">651,628</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <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;">3,063</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;">(1,197</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;">653,494</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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale 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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,967,847</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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,478</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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,435</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">
          <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; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,964,890</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;"><span style="text-decoration: underline;">Equity securities:</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">&#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; 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">&#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; 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">&#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; 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">&#160;</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;">Publicly traded equity securities included in other current assets (2)</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;">11,897</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;">236</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;">(5,832</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;">6,301</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;">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;" 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;">23,115</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;">25,001</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;">(5,125</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;">42,991</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 equity 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;">35,012</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;">25,237</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;">(10,957</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;">49,292</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: 4px;" 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 debt and equity securities</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;">2,002,859</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;">28,715</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;">(17,392</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 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; 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;">2,014,182</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>

<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; 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 sheets.</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; 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 publicly traded equity securities are
            included in other current assets. We recognize publicly traded equity securities at fair value. In the six months ended&#160;June 30, 2024, we recorded a $0.6
            million net unrealized gain in our condensed consolidated statements of operations related to changes 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; 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 privately held equity securities are included in deposits and other assets. We recognize our privately held 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, which are Level 3 inputs<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In the </span>six months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recorded a loss of $</span>2.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in our condensed consolidated statements of operations related to changes in the
              fair value of our investments in privately held companies.</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_DebtSecuritiesAvailableForSaleUnrealizedLossPositionFairValueTableTextBlock', 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 June 30, 2024 (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;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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;">440</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;">517,394</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;">(1,155</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;">142,390</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;">(1,288</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;">659,784</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;">(2,443</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%;" 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;">108</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;">173,618</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;">(482</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;">25,892</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;">(145</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;">199,510</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;">(627</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;" 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">
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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">
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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>

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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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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,240</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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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">
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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;">8,449</div>
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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;">(23</div>
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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>
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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;">9,319</div>
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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;">(27</div>
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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>
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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;">17,768</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;">(50</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>

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    <td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; 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 temporarily impaired securities</div>
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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">&#160;</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;">664</div>
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    <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>
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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;">1,260,824</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;">(2,522</div>
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    <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;">331,607</div>
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    <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>
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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;">(2,838</div>
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    <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>
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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;">1,592,431</div>
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    <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>
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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;">(5,360</div>
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    <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>
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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">6 Months Ended</th>
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<tr><th class="th"><div>Jun. 30, 2024</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_FairValueDisclosuresAbstract', window );"><strong>Fair Value Measurements [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_FairValueAssetsMeasuredOnRecurringBasisTextBlock', window );">Assets Measured at Fair Value on a Recurring Basis</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 tables present the major security types we held at June 30, 2024 and December 31, 2023 that we regularly measure and carry at fair
    value. 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 security&#8217;s fair value (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">

        </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; white-space: nowrap;" 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;">June 30, 2024</div>
        </td>

    <td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</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: 64%; 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;">Cash equivalents (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;">212,489</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;">212,489</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;">&#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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" 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 (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">&#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;">769,260</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;">769,260</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: 64%; 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;">236,580</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;">236,580</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: 64%;" 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 (3)</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;">776,021</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;">776,021</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: 64%; 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 (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;">19,715</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;">19,715</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: 64%; padding-bottom: 2px;" 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 (4)</div>
          </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;">6,854</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;">6,854</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;">&#8212;</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: 64%; padding-bottom: 4px; background-color: #CCEEFF;" 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; 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;">2,020,919</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;">995,364</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;">1,025,555</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="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">

        </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; white-space: nowrap;" 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, 2023</div>
        </td>

    <td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</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: 64%; 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;">Cash equivalents (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;">185,424</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">
          <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;">185,424</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">
          <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;">&#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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" 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 (5)</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;">801,228</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;">801,228</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: 64%; 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;">334,828</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;">334,828</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: 64%;" 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 (3)</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;">807,679</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;">807,679</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: 64%; 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 (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;">21,155</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;">21,155</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: 64%; padding-bottom: 2px;" 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 (4)</div>
          </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;">6,301</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;">6,301</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;">&#8212;</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: 64%; padding-bottom: 4px; background-color: #CCEEFF;" 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; 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;">2,156,615</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;">999,404</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;">1,157,211</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>

<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 sheets:</div>

<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; 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.</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; 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;">$16.9 million was included in cash and cash equivalents, with the difference included in short-term investments.</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; 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>

<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; 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;">Included in other current assets.</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; 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;">$33.0 million was included in cash and cash equivalents, with the difference included in short-term investments.</div>
        </td>

  </tr>


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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882585472">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stock-based Compensation Expense (Tables)<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
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<tr><th class="th"><div>Jun. 30, 2024</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;">The following table summarizes stock-based compensation expense for the three and six months ended&#160;June 30, 2024 and 2023 (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>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <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;">June 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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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">

        </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;">2024</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;">2023</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;">2024</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;">2023</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;">246</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;">118</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;">450</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;">237</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;">22,766</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;">19,249</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;">44,991</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;">38,816</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;">7,716</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;">7,194</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;">16,627</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;">14,457</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: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stock-based compensation expense</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;">30,728</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;">26,561</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;">62,068</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;">53,510</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="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">

        </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;">Six Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">June 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;">2024</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;">2023</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;">4.1</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;">3.6</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;">43.9</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;">47.3</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;">6.3 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>

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  <tr>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2024</div>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</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="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Liability Related to Sale of Future Royalties (Tables)<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
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<tr><th class="th"><div>Jun. 30, 2024</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;">The following table sets forth information on our liability related to sale of future royalties
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<div><br/>
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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;">Proceeds from sale of future royalties in January 2023</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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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">500,000</div>
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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: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance costs related to sale of future royalties</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;">(10,434</div>
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  </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;">Royalty payments to Royalty Pharma</div>
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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;">(44,628</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </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;">Interest expense related to sale of future royalties</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;">68,238</div>
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    <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; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties</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;">560</div>
        </td>

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  </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;">Net liability related to sale of future royalties as of December 31, 2023</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;">513,736</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; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty payments to Royalty Pharma</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">
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        </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">
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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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  <tr>

    <td style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
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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">
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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>

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  <tr>

    <td style="vertical-align: top; width: 88%; padding-bottom: 4px;" valign="bottom">
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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">
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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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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882442096">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Convertible Debt (Tables)<br></strong></div></th>
<th class="th" colspan="1">6 Months Ended</th>
</tr>
<tr><th class="th"><div>Jun. 30, 2024</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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75% Notes [Member]</a></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_ions_ConvertibleNotesDisclosureLineItems', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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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_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 June 30, 2024, we had the following
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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>

    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.75% 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>
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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>
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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;">575.0</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;">11.4</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_ac460e99cb6b43a8b64e987880ed0dd5">June 2028</span></div>
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    <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;">Interest rate</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;">1.75</div>
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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>

  </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;">Effective 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">
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        </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: 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;">53.73</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; width: 88%; background-color: #CCEEFF;" valign="bottom">
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        </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">
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        </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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<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% 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 Debt [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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At June 30, 2024, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes outstanding (in millions except interest rate and price
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<div><br/>
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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 style="vertical-align: top; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">0% 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;">632.5</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;">5.5</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_edbb9fb31e834f86ad026d22e567df04">April 2026</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; width: 88%;" 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; 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</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: top; width: 88%; 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; 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">
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        </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: 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>

  <tr>

    <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>

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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: 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">
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        </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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<span></span>
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<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_ConvertibleNotesDisclosureLineItems', window );"><strong>Convertible Debt [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_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 June 30, 2024, we had the following
    0.125% Notes outstanding with interest payable semi-annually (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%;">


  <tr>

    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px; white-space: nowrap;" 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">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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        </td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44.5</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">
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        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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        </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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        </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">
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  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
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        </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;">0.125</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>

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        </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>

  <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">
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        </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; width: 88%; background-color: #CCEEFF;" valign="bottom">
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        </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">
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        </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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion, excluding shares related to <span style="text-indent: 0pt;">0.125</span>% Notes that we have repurchased and are currently holding in 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;">0.5</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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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>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.</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>Tabular disclosure of convertible debt instrument. Includes, but is not limited to, principal amount and amortized premium or discount.</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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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Basis of Presentation (Details)<br></strong></div></th>
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<div>Jun. 30, 2024 </div>
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<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>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492883172384">
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<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Supplemental Financial Data, Inventories (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</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 [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">$ 24,623<span></span>
</td>
<td class="nump">$ 22,794<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">3,614<span></span>
</td>
<td class="nump">5,477<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">486<span></span>
</td>
<td class="nump">154<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 inventories</a></td>
<td class="nump">28,723<span></span>
</td>
<td class="nump">28,425<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 [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">22,211<span></span>
</td>
<td class="nump">20,985<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 [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">$ 2,412<span></span>
</td>
<td class="nump">$ 1,809<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_InventoryFinishedGoods">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">us-gaap_InventoryFinishedGoods</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/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483467/210-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">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_InventoryNetAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_InventoryNetAbstract</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>
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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_InventoryRawMaterials">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">us-gaap_InventoryRawMaterials</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_InventoryWorkInProcess">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">us-gaap_InventoryWorkInProcess</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_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember</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_PublicUtilitiesInventoryAxis=ions_CommercialRawMaterialsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_PublicUtilitiesInventoryAxis=ions_CommercialRawMaterialsMember</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>
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<head>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492980393040">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Supplemental Financial Data, Accrued Liabilities (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</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">$ 82,017<span></span>
</td>
<td class="nump">$ 105,967<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">10,603<span></span>
</td>
<td class="nump">7,454<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">4,583<span></span>
</td>
<td class="nump">4,875<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_OtherAccruedLiabilitiesCurrent', window );">Other miscellaneous expenses</a></td>
<td class="nump">17,127<span></span>
</td>
<td class="nump">29,598<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">$ 114,330<span></span>
</td>
<td class="nump">$ 147,894<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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">us-gaap_AccruedLiabilitiesCurrent</td>
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<tr>
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<td>xbrli:monetaryItemType</td>
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<tr>
<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>
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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_AccruedLiabilitiesCurrentAbstract</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>duration</td>
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<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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<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;">us-gaap_OtherAccruedLiabilitiesCurrent</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:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492879980624">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Revenues (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">6 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Jun. 30, 2024 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2024 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($) </div>
<div>Component </div>
<div>PerformanceObligation</div>
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</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 225,250<span></span>
</td>
<td class="nump">$ 188,411<span></span>
</td>
<td class="nump">$ 344,748<span></span>
</td>
<td class="nump">$ 318,935<span></span>
</td>
<td class="text">&#160;<span></span>
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</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_AstraZenecaCollaborationWainuaMember', window );">WAINUA (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>
</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_ContractWithCustomerAssetAndLiabilityAbstract', window );"><strong>Revenues [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_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="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="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 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="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="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="nump">55.00%<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_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>
<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_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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">72,036<span></span>
</td>
<td class="nump">77,897<span></span>
</td>
<td class="nump">$ 131,629<span></span>
</td>
<td class="nump">145,664<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_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>
<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_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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">56,743<span></span>
</td>
<td class="nump">61,012<span></span>
</td>
<td class="nump">95,198<span></span>
</td>
<td class="nump">111,258<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_WainusRoyaltiesMember', window );">WAINUA 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="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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">3,781<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">4,907<span></span>
</td>
<td class="nump">0<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_OtherCommercialMember', window );">Other 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>
<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_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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">11,512<span></span>
</td>
<td class="nump">16,885<span></span>
</td>
<td class="nump">31,524<span></span>
</td>
<td class="nump">34,406<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=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>
<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_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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">8,192<span></span>
</td>
<td class="nump">10,655<span></span>
</td>
<td class="nump">16,820<span></span>
</td>
<td class="nump">17,133<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_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>
<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_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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">3,320<span></span>
</td>
<td class="nump">6,230<span></span>
</td>
<td class="nump">14,704<span></span>
</td>
<td class="nump">17,273<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 );">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>
<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_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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">153,214<span></span>
</td>
<td class="nump">110,514<span></span>
</td>
<td class="nump">213,119<span></span>
</td>
<td class="nump">173,271<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_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>
<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_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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">141,524<span></span>
</td>
<td class="nump">91,013<span></span>
</td>
<td class="nump">190,870<span></span>
</td>
<td class="nump">129,347<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_WainuaJointDevelopmentRevenueMember', window );">WAINUA 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>
<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_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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">$ 11,690<span></span>
</td>
<td class="nump">$ 19,501<span></span>
</td>
<td class="nump">$ 22,249<span></span>
</td>
<td class="nump">$ 43,924<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_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_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_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_ContractWithCustomerAssetAndLiabilityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ContractWithCustomerAssetAndLiabilityAbstract</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_DisaggregationOfRevenueAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_DisaggregationOfRevenueAbstract</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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<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_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_AstraZenecaCollaborationWainuaMember</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_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>
</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_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_WainusRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_WainusRoyaltiesMember</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_OtherCommercialMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_OtherCommercialMember</td>
</tr>
<tr>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492877705024">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, AstraZeneca (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">6 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Jun. 30, 2024 </div>
<div>USD ($) </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Jun. 30, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2024 </div>
<div>USD ($) </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Jun. 30, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 225,250<span></span>
</td>
<td class="nump">$ 188,411<span></span>
</td>
<td class="nump">$ 344,748<span></span>
</td>
<td class="nump">$ 318,935<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_AstrazenecaCollaborationsMember', window );">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>
</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_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="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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 15,960<span></span>
</td>
<td class="nump">$ 59,501<span></span>
</td>
<td class="nump">$ 27,645<span></span>
</td>
<td class="nump">$ 83,926<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 contract revenue</a></td>
<td class="nump">$ 1,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,900<span></span>
</td>
<td class="text">&#160;<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_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember', window );">AstraZeneca [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">7.00%<span></span>
</td>
<td class="nump">32.00%<span></span>
</td>
<td class="nump">8.00%<span></span>
</td>
<td class="nump">26.00%<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_AstrazenecaCollaborationsMember', window );">AstraZeneca [Member] | Minimum [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">$ 920,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 920,000<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_AstraZenecaCollaborationWainuaMember', window );">WAINUA [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_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="nump">1<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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="nump">$ 3,600,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 3,600,000<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_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration', window );">Maximum amount of upfront payments over term of collaboration</a></td>
<td class="nump">200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">200,000<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_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="nump">485,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">485,000<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_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="nump">2,900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,900,000<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_AstraZenecaCollaborationWainuaMember', window );">WAINUA [Member] | Minimum [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_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="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_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="nump">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 30,000<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_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember', window );">Cardiovascular, Renal and Metabolic Diseases [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_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="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_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 development milestone payments to be received over the term of the collaboration.</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_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration</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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 the Company is eligible to receive over the term of the collaboration.</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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</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_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 sales milestone payments to be received over the term of the collaboration.</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_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</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_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 upfront payments to be received over the term of the collaboration.</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_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration</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_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 payment to be achieved 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_NextPaymentToBeAchieved</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_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_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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<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;">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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<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_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember">
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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>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
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<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>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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<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_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
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<td>na</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_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember</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_TypeOfArrangementAxis=ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember</td>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492877568400">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Biogen (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">6 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</div></th>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</div></th>
<th class="th"><div>Dec. 31, 2023</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_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">$ 225,250<span></span>
</td>
<td class="nump">$ 188,411<span></span>
</td>
<td class="nump">$ 344,748<span></span>
</td>
<td class="nump">$ 318,935<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 [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">138,159<span></span>
</td>
<td class="nump">$ 97,402<span></span>
</td>
<td class="nump">197,395<span></span>
</td>
<td class="nump">$ 167,903<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 contract revenue</a></td>
<td class="nump">$ 241,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 241,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 307,400<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 [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="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_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">61.00%<span></span>
</td>
<td class="nump">52.00%<span></span>
</td>
<td class="nump">57.00%<span></span>
</td>
<td class="nump">53.00%<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 [Member] | Minimum [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_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 3,900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 3,900,000<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_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology [Member] | QALSODY [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_NextPaymentToBeAchieved', window );">Next payment to be achieved</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>
<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">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>
</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_BiogenCollaboration2012NeurologyMember', window );">2012 Neurology [Member] | ION582 [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">30,000<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="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_BiogenCollaboration2012NeurologyMember', window );">2012 Neurology [Member] | IONIS-MAPT [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_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 25,000<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>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next payment to be achieved 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_NextPaymentToBeAchieved</td>
</tr>
<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 );">- 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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</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_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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<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;">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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<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_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>
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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>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<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_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>
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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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<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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_MinimumMember</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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<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_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>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_QalsodyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_QalsodyMember</td>
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<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>
<td></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_TypeOfArrangementAxis=ions_BiogenCollaboration2012NeurologyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_BiogenCollaboration2012NeurologyMember</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>
</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>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_Ion582Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_Ion582Member</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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<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;">srt_ProductOrServiceAxis=ions_IonisMaptMember</td>
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<tr>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492879980624">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Otsuka (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">6 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Jun. 30, 2024 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Jun. 30, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2024 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Jun. 30, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 225,250<span></span>
</td>
<td class="nump">$ 188,411<span></span>
</td>
<td class="nump">$ 344,748<span></span>
</td>
<td class="nump">$ 318,935<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_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [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_UpfrontPaymentReceived', window );">Upfront payment received</a></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>
</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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="nump">290,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">290,000<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_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration', window );">Maximum amount of upfront payments over term of collaboration</a></td>
<td class="nump">85,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">85,000<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_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="nump">65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">65,000<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_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="nump">140,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">140,000<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_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 85,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 85,000<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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="nump">2<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="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="nump">$ 20,000<span></span>
</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>
</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">18,905<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">19,691<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_ContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="nump">$ 8,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 8,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 8,500<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_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [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="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_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">8.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">6.00%<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_TypeOfArrangementAxis=ions_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [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_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="nump">30.00%<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_TypeOfArrangementAxis=ions_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [Member] | Donidalorsen [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_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="nump">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 15,000<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_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [Member] | License of Donidalorsen [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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">17,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">17,500<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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">17,500<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>
</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_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [Member] | R&amp;D Services for Donidalorsen [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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 2,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,500<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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 the Company is eligible to receive over the term of the collaboration.</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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</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_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 regulatory milestone payments to be received over the term of the collaboration.</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_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</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_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 sales milestone payments to be received over the term of the collaboration.</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_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</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_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 upfront payments to be received over the term of the collaboration.</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_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration</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_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 payment to be achieved 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_NextPaymentToBeAchieved</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_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_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_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_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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<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;">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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<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_TypeOfArrangementAxis=ions_OtsukaPharmaceuticalCoLtdCollaborationMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_OtsukaPharmaceuticalCoLtdCollaborationMember</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>
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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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<tr>
<td><strong> Period Type:</strong></td>
<td></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;">srt_RangeAxis=srt_MaximumMember</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>
<td></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>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_DonidalorsenMember</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>
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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;">srt_ProductOrServiceAxis=ions_LicenseOfDonidalorsenMember</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></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;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesForDonidalorsenMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>na</td>
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<td><strong> Period Type:</strong></td>
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<DOCUMENT>
<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
<title></title>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492876892096">
<tr>
<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="2">3 Months Ended</th>
<th class="th" colspan="2">6 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Jun. 30, 2024 </div>
<div>USD ($) </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Jun. 30, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2024 </div>
<div>USD ($) </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Jun. 30, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jul. 31, 2024 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</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_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">$ 225,250<span></span>
</td>
<td class="nump">$ 188,411<span></span>
</td>
<td class="nump">$ 344,748<span></span>
</td>
<td class="nump">$ 318,935<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_RocheCollaborationsMember', window );">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">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3<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">$ 11,089<span></span>
</td>
<td class="nump">$ 5,754<span></span>
</td>
<td class="nump">$ 22,595<span></span>
</td>
<td class="nump">$ 8,121<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_ContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="nump">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 36,700<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 [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="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_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">5.00%<span></span>
</td>
<td class="nump">3.00%<span></span>
</td>
<td class="nump">7.00%<span></span>
</td>
<td class="nump">3.00%<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_TypeOfArrangementAxis=ions_RocheCollaborationsMember', window );">Roche [Member] | Minimum [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_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 345,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 345,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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 );">HD [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">1<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>
<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 );">IONIS-FB-L for Complement-Mediated Diseases [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="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>
</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 );">IONIS-FB-L for Complement-Mediated Diseases [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>
<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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</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">$ 430,000<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_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</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">35,000<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_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</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">25,000<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_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</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">90,000<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_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</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">280,000<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_NextPaymentToBeAchieved', window );">Next payment to be achieved</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">$ 23,500<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_RocheCollaborationRNATargetedProgramsForADAndHDMember', window );">RNA-targeted Programs for AD and HD [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">1<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>
<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_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 development milestone payments to be received over the term of the collaboration.</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_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration</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_MaximumAmountOfLicenseFeesOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 license fees to be received over the term of the collaboration.</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_MaximumAmountOfLicenseFeesOverTermOfCollaboration</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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 the Company is eligible to receive over the term of the collaboration.</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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</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_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 regulatory milestone payments to be received over the term of the collaboration.</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_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</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_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 sales milestone payments to be received over the term of the collaboration.</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_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</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_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 payment to be achieved 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_NextPaymentToBeAchieved</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_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_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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482861/275-10-50-20<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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479837/606-10-45-2<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;">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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-41<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479941/924-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-5<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-30<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-42<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-40<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-4<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>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember</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_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</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_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
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<tr>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember</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_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember</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_TypeOfArrangementAxis=ions_RocheCollaborationRNATargetedProgramsForADAndHDMember</td>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492876876528">
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<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Basic and Diluted Net Loss Per Share (Details)<br></strong></div></th>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Jun. 30, 2023</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="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>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
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<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="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_EarningsPerShareDilutedAbstract', window );"><strong>Diluted Net Loss per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<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">0.125%<span></span>
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<td class="nump">0.125%<span></span>
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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://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<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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<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 );">- 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_ConvertibleSeniorNotes175PercentMember</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>
</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>
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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>
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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>
<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_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>
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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>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>55
<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">
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<body>
<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492880542528">
<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">6 Months Ended</th>
</tr>
<tr><th class="th"><div>Jun. 30, 2024</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">75.00%<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">21.00%<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">4.00%<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">96.00%<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>
</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_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
</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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<td><strong> Period Type:</strong></td>
<td>instant</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_ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td>dtr-types:percentItemType</td>
</tr>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<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_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
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<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
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<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>
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<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>
</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_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>
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<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>
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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>
</div></td></tr>
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<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>
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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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<td><strong> Period Type:</strong></td>
<td>duration</td>
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</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>56
<FILENAME>R44.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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</head>
<body>
<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882705952">
<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">6 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Jun. 30, 2024 </div>
<div>USD ($) </div>
<div>Company</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</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">7<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 Debt 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">$ 1,343,698<span></span>
</td>
<td class="nump">$ 1,316,219<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">67<span></span>
</td>
<td class="nump">415<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">(3,026)<span></span>
</td>
<td class="num">(5,238)<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">1,340,739<span></span>
</td>
<td class="nump">1,311,396<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 Debt 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">462,896<span></span>
</td>
<td class="nump">651,628<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">275<span></span>
</td>
<td class="nump">3,063<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">(2,334)<span></span>
</td>
<td class="num">(1,197)<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">460,837<span></span>
</td>
<td class="nump">653,494<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_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Available-for-sale Debt 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">1,806,594<span></span>
</td>
<td class="nump">1,967,847<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">342<span></span>
</td>
<td class="nump">3,478<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">(5,360)<span></span>
</td>
<td class="num">(6,435)<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">1,801,576<span></span>
</td>
<td class="nump">1,964,890<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">35,012<span></span>
</td>
<td class="nump">35,012<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">25,335<span></span>
</td>
<td class="nump">25,237<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">(12,470)<span></span>
</td>
<td class="num">(10,957)<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">47,877<span></span>
</td>
<td class="nump">49,292<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 Debt 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">1,841,606<span></span>
</td>
<td class="nump">2,002,859<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">25,677<span></span>
</td>
<td class="nump">28,715<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">(17,830)<span></span>
</td>
<td class="num">(17,392)<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">1,849,453<span></span>
</td>
<td class="nump">2,014,182<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 Debt 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">552,837<span></span>
</td>
<td class="nump">559,967<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">36<span></span>
</td>
<td class="nump">157<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">(1,569)<span></span>
</td>
<td class="num">(2,625)<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">551,304<span></span>
</td>
<td class="nump">557,499<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 Debt 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">218,639<span></span>
</td>
<td class="nump">243,151<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">191<span></span>
</td>
<td class="nump">1,270<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">(874)<span></span>
</td>
<td class="num">(692)<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">217,956<span></span>
</td>
<td class="nump">243,729<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 Debt 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">121,781<span></span>
</td>
<td class="nump">224,711<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">5<span></span>
</td>
<td class="nump">64<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">(310)<span></span>
</td>
<td class="num">(611)<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">121,476<span></span>
</td>
<td class="nump">224,164<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 Debt 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">115,349<span></span>
</td>
<td class="nump">110,138<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">72<span></span>
</td>
<td class="nump">547<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">(317)<span></span>
</td>
<td class="num">(21)<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">115,104<span></span>
</td>
<td class="nump">110,664<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 Debt 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">650,997<span></span>
</td>
<td class="nump">513,784<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">12<span></span>
</td>
<td class="nump">152<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">(1,105)<span></span>
</td>
<td class="num">(1,889)<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">649,904<span></span>
</td>
<td class="nump">512,047<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 Debt 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">127,240<span></span>
</td>
<td class="nump">294,873<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">12<span></span>
</td>
<td class="nump">1,239<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">(1,135)<span></span>
</td>
<td class="num">(480)<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">126,117<span></span>
</td>
<td class="nump">295,632<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 Debt 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">18,083<span></span>
</td>
<td class="nump">17,757<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">14<span></span>
</td>
<td class="nump">42<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">(42)<span></span>
</td>
<td class="num">(113)<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">18,055<span></span>
</td>
<td class="nump">17,686<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 Debt 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">1,668<span></span>
</td>
<td class="nump">3,466<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">0<span></span>
</td>
<td class="nump">7<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">(8)<span></span>
</td>
<td class="num">(4)<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">1,660<span></span>
</td>
<td class="nump">3,469<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="ro">
<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="reu">
<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">11,897<span></span>
</td>
<td class="nump">11,897<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_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">334<span></span>
</td>
<td class="nump">236<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_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(5,377)<span></span>
</td>
<td class="num">(5,832)<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 );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">6,854<span></span>
</td>
<td class="nump">6,301<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_InvestmentsDebtAndEquitySecuritiesAbstract', window );"><strong>Available-for-sale Debt 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="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedGain', window );">Unrealized gain on equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">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_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="ro">
<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="reu">
<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">23,115<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_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">25,001<span></span>
</td>
<td class="nump">25,001<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_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(7,093)<span></span>
</td>
<td class="num">(5,125)<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 );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">41,023<span></span>
</td>
<td class="nump">$ 42,991<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_InvestmentsDebtAndEquitySecuritiesAbstract', window );"><strong>Available-for-sale Debt 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="ro">
<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 securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">$ (2,000)<span></span>
</td>
<td class="text">&#160;<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 sheets.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Our publicly traded equity securities are
            included in other current assets. We recognize publicly traded equity securities at fair value. In the six months ended&#160;June 30, 2024, we recorded a $0.6
            million net unrealized gain in our condensed consolidated statements of operations related to changes 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 privately held equity securities are included in deposits and other assets. We recognize our privately held 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, which are Level 3 inputs<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In the </span>six months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>June 30, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recorded a loss of $</span>2.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in our condensed consolidated statements of operations related to changes in the
              fair value of our investments in privately held companies.</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>
</table>
<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>
<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_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>
</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_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>
</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_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>
</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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<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;">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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<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;">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> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<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;">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/exampleRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 103<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482078/820-10-55-103<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 100<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482078/820-10-55-100<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481830/320-10-45-1<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<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;">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> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481830/320-10-45-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<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;">us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent</td>
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<tr>
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<td>us-gaap_</td>
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<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> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481830/320-10-45-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(12))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<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;">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>
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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>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<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> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<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;">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/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<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;">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>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtSecuritiesCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_DebtSecuritiesCurrentAbstract</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_DebtSecuritiesNoncurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_DebtSecuritiesNoncurrentAbstract</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_EquitySecuritiesFVNIAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_EquitySecuritiesFVNIAbstract</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_EquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483467/210-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482736/825-10-45-1A<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_EquitySecuritiesFvNi</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_EquitySecuritiesFvNiCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>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>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<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;">us-gaap_EquitySecuritiesFvNiCost</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_EquitySecuritiesFvNiUnrealizedGain">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 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>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 321<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479536/321-10-50-4<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_EquitySecuritiesFvNiUnrealizedGain</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_EquitySecuritiesFvNiUnrealizedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 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> -Topic 321<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479536/321-10-50-4<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_EquitySecuritiesFvNiUnrealizedLoss</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_InvestmentsAllOtherInvestmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_InvestmentsAllOtherInvestmentsAbstract</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_InvestmentsDebtAndEquitySecuritiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_InvestmentsDebtAndEquitySecuritiesAbstract</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_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember</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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<tr>
<td><strong> Period Type:</strong></td>
<td></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_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember</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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember</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>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>
<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_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember</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_FinancialInstrumentAxis=ions_EquitySecuritiesPubliclyTradedCompaniesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_FinancialInstrumentAxis=ions_EquitySecuritiesPubliclyTradedCompaniesMember</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_FinancialInstrumentAxis=ions_EquitySecuritiesPrivateCompaniesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_FinancialInstrumentAxis=ions_EquitySecuritiesPrivateCompaniesMember</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>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882259952">
<tr>
<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>Jun. 30, 2024 </div>
<div>USD ($) </div>
<div>Investment</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">664<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 1,260,824<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">331,607<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">1,592,431<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">(2,522)<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">(2,838)<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">$ (5,360)<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">440<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">$ 517,394<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">142,390<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_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">659,784<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">(1,155)<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">(1,288)<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">$ (2,443)<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">108<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">$ 173,618<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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">25,892<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">199,510<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">(482)<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">(145)<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">$ (627)<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">71<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">$ 561,363<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">154,006<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">715,369<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">(862)<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">(1,378)<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">$ (2,240)<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">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_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">$ 8,449<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">9,319<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">17,768<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">(23)<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">(27)<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">$ (50)<span></span>
</td>
</tr>
</table>
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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_AvailableForSaleSecuritiesAbstract</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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract</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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract</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>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/exampleRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479081/326-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-7<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-5<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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger</td>
</tr>
<tr>
<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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 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://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-7<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-5<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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss</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 );">- 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/exampleRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479081/326-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-7<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-5<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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months</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>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></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>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://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-7<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-5<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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss</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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 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> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-4<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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions</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>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>
<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> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479081/326-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-6<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-4<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_DebtSecuritiesAvailableForSaleUnrealizedLossPosition</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</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>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>
<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/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-6<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479106/326-30-50-4<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_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss</td>
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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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<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember</td>
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<DOCUMENT>
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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">
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882081120">
<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>Jun. 30, 2024</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Jun. 30, 2023</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">$ 1,801,576<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 1,964,890<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">$ 47,877<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 49,292<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_ConvertibleSeniorNotes175PercentMember', window );">1.75% 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">1.75%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.75%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.75%<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_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_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="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_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 6,854<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 6,301<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="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_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">212,489<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">185,424<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,020,919<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">2,156,615<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="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">769,260<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">801,228<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="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">16,900<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">33,000<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="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>[4]</sup></td>
<td class="nump">236,580<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">334,828<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 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>[4]</sup></td>
<td class="nump">776,021<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">807,679<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="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>[4]</sup></td>
<td class="nump">19,715<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">21,155<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="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_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="nump">6,854<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,301<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="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_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">212,489<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">185,424<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">995,364<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">999,404<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="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 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">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="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">776,021<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">807,679<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="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">6,854<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,301<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">1,025,555<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,157,211<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] | 1.75% 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 );">Convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">634,400<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">661,100<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] | 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 );">Convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">649,600<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">667,800<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] | 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 );">Convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">43,400<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">42,400<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="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">769,260<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">801,228<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="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">236,580<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">334,828<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="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 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="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">19,715<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">21,155<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><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.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">$16.9 million was included in cash and cash equivalents, with the difference included in short-term investments.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">$33.0 million was included in cash and cash equivalents, with the difference 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">Included in short-term investments.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[5]</td>
<td style="vertical-align: top;" valign="top">Included in other current assets.</td>
</tr>
</table></td></tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AssetsFairValueDisclosure">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Fair value portion of asset recognized for present right to economic benefit.</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> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 100<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482078/820-10-55-100<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<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).</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> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 103<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482078/820-10-55-103<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 100<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482078/820-10-55-100<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481800/320-10-50-2<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481830/320-10-45-1<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479130/326-30-45-1<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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure">
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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>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<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>
<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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br></p></div>
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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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483467/210-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482736/825-10-45-1A<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>
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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>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492885526240">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stock-based Compensation Expense (Details) - USD ($)<br> $ / shares in Units, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">6 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</div></th>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</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="text">&#160;<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="nump">$ 30,728<span></span>
</td>
<td class="nump">$ 26,561<span></span>
</td>
<td class="nump">$ 62,068<span></span>
</td>
<td class="nump">$ 53,510<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="text">&#160;<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="text">&#160;<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="nump">246<span></span>
</td>
<td class="nump">118<span></span>
</td>
<td class="nump">450<span></span>
</td>
<td class="nump">237<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="text">&#160;<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="text">&#160;<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="nump">22,766<span></span>
</td>
<td class="nump">19,249<span></span>
</td>
<td class="nump">44,991<span></span>
</td>
<td class="nump">38,816<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="text">&#160;<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="text">&#160;<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="nump">7,716<span></span>
</td>
<td class="nump">$ 7,194<span></span>
</td>
<td class="nump">16,627<span></span>
</td>
<td class="nump">$ 14,457<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="text">&#160;<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="text">&#160;<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="nump">61,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 61,600<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year 3 months 18 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] | Employees [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4.10%<span></span>
</td>
<td class="nump">3.60%<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="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">43.90%<span></span>
</td>
<td class="nump">47.30%<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="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">6 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_EmployeeStockMember', window );">ESPP [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5.30%<span></span>
</td>
<td class="nump">5.20%<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="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">38.40%<span></span>
</td>
<td class="nump">36.70%<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="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="text">&#160;<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="text">&#160;<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="nump">96,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 96,700<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year 7 months 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_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Employees [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 52.6<span></span>
</td>
<td class="nump">$ 39.5<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="text">&#160;<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="text">&#160;<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="nump">$ 13,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 13,800<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year 10 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_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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="re">
<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)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 78.41<span></span>
</td>
<td class="nump">$ 58.99<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] | Granted in 2024 [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></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>
</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="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="ro">
<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)</a></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="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] | Granted in 2024 [Member] | Minimum [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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="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="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] | Granted in 2024 [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>
</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="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">200.00%<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] | Granted in 2023 [Member] | Executive Officers [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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="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="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>
</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="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)</a></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="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] | Granted in 2023 [Member] | Executive Officers [Member] | Minimum [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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 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="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] | Granted in 2023 [Member] | Executive Officers [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>
</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="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">200.00%<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_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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.F)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479830/718-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (h)(1)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<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;">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>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
</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>
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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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
</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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1</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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
<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_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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iv)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<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;">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_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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480429/718-10-50-2<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;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1</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_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>
</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_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>
</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_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>
</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_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>
</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_GranteeStatusAxis=us-gaap_ShareBasedPaymentArrangementEmployeeMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_GranteeStatusAxis=us-gaap_ShareBasedPaymentArrangementEmployeeMember</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_AwardTypeAxis=us-gaap_EmployeeStockMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_EmployeeStockMember</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_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_RestrictedStockUnitsRSUMember</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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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<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_AwardTypeAxis=us-gaap_PerformanceSharesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_PerformanceSharesMember</td>
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<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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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GranteeStatusAxis=srt_ExecutiveOfficerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_GranteeStatusAxis=srt_ExecutiveOfficerMember</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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<td><strong> Balance Type:</strong></td>
<td></td>
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<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_AwardDateAxis=ions_GrantedIn2024Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_AwardDateAxis=ions_GrantedIn2024Member</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>
</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_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_MinimumMember</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>
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<td><strong> Balance Type:</strong></td>
<td></td>
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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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<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>
</tr>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
<td></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_AwardDateAxis=ions_GrantedIn2023Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_AwardDateAxis=ions_GrantedIn2023Member</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>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
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<DOCUMENT>
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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;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492985367552">
<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">6 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</div></th>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</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_IncomeTaxDisclosureAbstract', window );"><strong>Income Taxes [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_IncomeTaxExpenseBenefit', window );">Income tax expense</a></td>
<td class="nump">$ 64<span></span>
</td>
<td class="nump">$ 7,842<span></span>
</td>
<td class="nump">$ 140<span></span>
</td>
<td class="nump">$ 19,223<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_IncomeTaxDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_IncomeTaxDisclosureAbstract</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_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> -Topic 270<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482964/270-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (ee)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-32<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-12<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 231<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482663/740-10-55-231<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-9<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479360/740-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-8<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482685/740-10-50-10<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482810/280-10-50-22<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477250/944-220-S99-1<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -SubTopic 20<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482659/740-20-45-2<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -SubTopic 10<br> -Topic 235<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480678/235-10-S99-1<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;">us-gaap_IncomeTaxExpenseBenefit</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: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>
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<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;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492882686560">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Liability Related to Sale of Future Royalties (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="2">6 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Jan. 31, 2023</div></th>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</div></th>
<th class="th"><div>Dec. 31, 2023</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_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ProceedsFromSaleOfFutureRoyalties', window );">Proceeds from sale of future royalties in January 2023</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 500,000<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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Issuance costs related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,434)<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_RoyaltyPayments', window );">Royalty payments to Royalty Pharma</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(16,236)<span></span>
</td>
<td class="num">(12,562)<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_InterestExpenseRelatedToSaleOfFutureRoyalties', window );">Interest expense related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">35,949<span></span>
</td>
<td class="nump">$ 32,915<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_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Net liability related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">533,754<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 513,736<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_RoyaltyPurchaseAgreementMember', window );">Royalty Purchase Agreement [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_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [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="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontRoyaltyPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_MaximumAmountOfPaymentsReceivableForAdditionalMilestones', window );">Maximum amount of payments receivable for additional milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 625,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" 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="nump">13.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ProceedsFromSaleOfFutureRoyalties', window );">Proceeds from sale of future royalties in January 2023</a></td>
<td class="nump">$ 500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Issuance costs related to sale of future royalties</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="num">(10,434)<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_RoyaltyPayments', window );">Royalty payments to Royalty Pharma</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (16,236)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(44,628)<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_InterestExpenseRelatedToSaleOfFutureRoyalties', window );">Interest expense related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">35,949<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">68,238<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_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties', window );">Amortization of issuance costs related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">305<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">560<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_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Net liability related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">533,754<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 513,736<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_RoyaltyPurchaseAgreementMember', window );">Royalty Purchase Agreement [Member] | SPINRAZA [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_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid', window );">Maximum amount of annual sales on which royalty payments are paid</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,500,000<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_RoyaltyPurchaseAgreementMember', window );">Royalty Purchase Agreement [Member] | SPINRAZA [Member] | Minimum [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_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [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="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid on annual sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<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_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack', window );">Maximum royalty payments made before royalty interest reverts back</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 475,000<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_RoyaltyPurchaseAgreementMember', window );">Royalty Purchase Agreement [Member] | SPINRAZA [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>
</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_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [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="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid on annual sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45.00%<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_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack', window );">Maximum royalty payments made before royalty interest reverts back</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 550,000<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_RoyaltyPurchaseAgreementMember', window );">Royalty Purchase Agreement [Member] | Pelacarsen [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_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [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="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid on annual sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<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_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 the sale of future royalties.</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_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties</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_ions_InterestExpenseRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 interest expense using the effective interest rate method related to the sale of future royalties.</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_InterestExpenseRelatedToSaleOfFutureRoyalties</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_ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 the unamortized liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate 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_LiabilityRelatedToSaleOfFutureRoyaltiesNet</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_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 annual sales on which royalty payments are paid under the royalty purchase 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_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid</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_MaximumAmountOfPaymentsReceivableForAdditionalMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 additional milestones under the royalty purchase 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_MaximumAmountOfPaymentsReceivableForAdditionalMilestones</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_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>Maximum royalty payments under the royalty purchase agreement made before royalty interest reverts back to the Company.</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_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack</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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 for transaction costs in connection with a monetization transaction of future SPINRAZA and pelacarsen royalties the Company is entitled to under collaboration and licensing agreements.</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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties</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_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 royalty payments paid on annual sales of medicine.</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_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine</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_ProceedsFromSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 future royalties under a royalty purchase 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_ProceedsFromSaleOfFutureRoyalties</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_ions_RoyaltyPayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 royalty payments made during the period under a royalty purchase 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_RoyaltyPayments</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>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_RoyaltyRevenueMonetizationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_RoyaltyRevenueMonetizationAbstract</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_UpfrontRoyaltyPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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 royalty purchase 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_UpfrontRoyaltyPaymentReceived</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_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/exampleRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482949/835-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482900/835-30-50-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-2<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-6<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>
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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_RoyaltyPurchaseAgreementMember</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>
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<td><strong> Name:</strong></td>
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<td><strong> Name:</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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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_PelacarsenMember</td>
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<span style="display: none;">v3.24.2.u1</span><table class="report" border="0" cellspacing="2" id="idm140492880741008">
<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="2">6 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Jun. 30, 2024</div></th>
<th class="th"><div>Jun. 30, 2023</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</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>
</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 senior notes</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 420,158<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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75% 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_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>
</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="text">&#160;<span></span>
</td>
<td class="nump">$ 575,000<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_RepaymentsOfConvertibleDebt', window );">Repurchase of convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 488,200<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="nump">575,000<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" 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="nump">$ 11,400<span></span>
</td>
<td class="text">&#160;<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_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="text">Jun. 30,  2028<span></span>
</td>
<td class="text">&#160;<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="nump">1.75%<span></span>
</td>
<td class="nump">1.75%<span></span>
</td>
<td class="nump">1.75%<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_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="nump">2.30%<span></span>
</td>
<td class="text">&#160;<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_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="nump">$ 53.73<span></span>
</td>
<td class="text">&#160;<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_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="nump">10.7<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>
</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="nump">100.00%<span></span>
</td>
<td class="text">&#160;<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_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>
</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>
</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="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>
</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="nump">$ 5,500<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>
</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">Apr. 30,  2026<span></span>
</td>
<td class="text">&#160;<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="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<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_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="nump">0.50%<span></span>
</td>
<td class="text">&#160;<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_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="nump">$ 57.84<span></span>
</td>
<td class="text">&#160;<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_DebtInstrumentConvertibleConversionPriceIncludingCallSpread', window );">Effective conversion price per share with call spread (in dollars per share)</a></td>
<td class="nump">$ 76.39<span></span>
</td>
<td class="text">&#160;<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_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="nump">10.9<span></span>
</td>
<td class="text">&#160;<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_CallSpread', window );">Cost of call spread</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">$ 46,900<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">136,700<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 89,800<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="nump">100.00%<span></span>
</td>
<td class="text">&#160;<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_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>
</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>
</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 senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 504,400<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_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="nump">$ 44,500<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>
</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="nump">$ 100<span></span>
</td>
<td class="text">&#160;<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_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="text">Dec. 31,  2024<span></span>
</td>
<td class="text">&#160;<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_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</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="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_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="nump">0.50%<span></span>
</td>
<td class="text">&#160;<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_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="nump">$ 83.28<span></span>
</td>
<td class="text">&#160;<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_DebtInstrumentConvertibleConversionPriceIncludingCallSpread', window );">Effective conversion price per share with call spread (in dollars per share)</a></td>
<td class="nump">$ 123.38<span></span>
</td>
<td class="text">&#160;<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_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="nump">0.5<span></span>
</td>
<td class="text">&#160;<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_CallSpread', window );">Cost of call spread</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">$ 52,600<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_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</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">108,700<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_ProceedsFromIssuanceOfWarrants', window );">Proceeds from issuance of warrants</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">$ 56,100<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="nump">100.00%<span></span>
</td>
<td class="text">&#160;<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://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-4<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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-5<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/exampleRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482949/835-30-55-8<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69B<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481568/470-20-55-69B<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69C<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481568/470-20-55-69C<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482900/835-30-50-1<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-2<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;">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/exampleRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482949/835-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482900/835-30-50-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-2<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-6<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://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<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/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22)(a)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1B<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_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> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1A<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-1A<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482925/835-30-45-2<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482900/835-30-50-1<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1D<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481139/470-20-50-1D<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_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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 27<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-27<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_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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-14<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_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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482740/230-10-45-15<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>
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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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<td><strong> Name:</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>
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<SEQUENCE>63
<FILENAME>Financial_Report.xlsx
<DESCRIPTION>IDEA: XBRL DOCUMENT
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end
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>64
<FILENAME>Show.js
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
// Edgar(tm) Renderer was created by staff of the U.S. Securities and Exchange Commission.  Data and content created by government employees within the scope of their employment are not subject to domestic copyright protection. 17 U.S.C. 105.
var Show={};Show.LastAR=null,Show.showAR=function(a,r,w){if(Show.LastAR)Show.hideAR();var e=a;while(e&&e.nodeName!='TABLE')e=e.nextSibling;if(!e||e.nodeName!='TABLE'){var ref=((window)?w.document:document).getElementById(r);if(ref){e=ref.cloneNode(!0);
e.removeAttribute('id');a.parentNode.appendChild(e)}}
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e.style.display=d;if(a.textContent){a.textContent=p+a.textContent.substring(1)}else{a.innerText=p+a.innerText.substring(1)}}}
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>65
<FILENAME>report.css
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
/* Updated 2009-11-04 */
/* v2.2.0.24 */

/* DefRef Styles */
..report table.authRefData{
	background-color: #def;
	border: 2px solid #2F4497;
	font-size: 1em;
	position: absolute;
}

..report table.authRefData a {
	display: block;
	font-weight: bold;
}

..report table.authRefData p {
	margin-top: 0px;
}

..report table.authRefData .hide {
	background-color: #2F4497;
	padding: 1px 3px 0px 0px;
	text-align: right;
}

..report table.authRefData .hide a:hover {
	background-color: #2F4497;
}

..report table.authRefData .body {
	height: 150px;
	overflow: auto;
	width: 400px;
}

..report table.authRefData table{
	font-size: 1em;
}

/* Report Styles */
..pl a, .pl a:visited {
	color: black;
	text-decoration: none;
}

/* table */
..report {
	background-color: white;
	border: 2px solid #acf;
	clear: both;
	color: black;
	font: normal 8pt Helvetica, Arial, san-serif;
	margin-bottom: 2em;
}

..report hr {
	border: 1px solid #acf;
}

/* Top labels */
..report th {
	background-color: #acf;
	color: black;
	font-weight: bold;
	text-align: center;
}

..report th.void	{
	background-color: transparent;
	color: #000000;
	font: bold 10pt Helvetica, Arial, san-serif;
	text-align: left;
}

..report .pl {
	text-align: left;
	vertical-align: top;
	white-space: normal;
	width: 200px;
	white-space: normal; /* word-wrap: break-word; */
}

..report td.pl a.a {
	cursor: pointer;
	display: block;
	width: 200px;
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}

..report td.pl div.a {
	width: 200px;
}

..report td.pl a:hover {
	background-color: #ffc;
}

/* Header rows... */
..report tr.rh {
	background-color: #acf;
	color: black;
	font-weight: bold;
}

/* Calendars... */
..report .rc {
	background-color: #f0f0f0;
}

/* Even rows... */
..report .re, .report .reu {
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}

..report .reu td {
	border-bottom: 1px solid black;
}

/* Odd rows... */
..report .ro, .report .rou {
	background-color: white;
}

..report .rou td {
	border-bottom: 1px solid black;
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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; Organization and 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; font-weight: bold;"&gt;Organization and Business Activity&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 incorporated in California on January 10, 1989. In conjunction with our initial public offering, we reorganized as a Delaware
    corporation in April 1991. We are a leader in the discovery and development of RNA-targeted therapeutics.&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;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 six months ended&#160;June 30, 2024 and 2023 on the same basis as the audited financial statements for the year ended December 31, 2023. 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, 2023 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;

&lt;div&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_d751d8638e404708bbf18fb6bb90a9f5"&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 &lt;span style="-sec-ix-hidden:Fact_baf534ae803246ddb035eb980683637d"&gt;single&lt;/span&gt;
    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: justify; 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 United States, or &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;
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&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 six months ended&#160;June 30, 2024 and 2023 on the same basis as the audited financial statements for the year ended December 31, 2023. 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, 2023 included in our Annual
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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="display:none;"&gt;&lt;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_d751d8638e404708bbf18fb6bb90a9f5"&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 &lt;span style="-sec-ix-hidden:Fact_baf534ae803246ddb035eb980683637d"&gt;single&lt;/span&gt;
    operating segment.&lt;/div&gt;
</us-gaap:SegmentReportingPolicyPolicyTextBlock>
    <us-gaap:UseOfEstimates
      contextRef="c20240101to20240630"
      id="Text_a36e2aeec70b4cda8a724e271f28212e">
&lt;div style="display:none;"&gt;&lt;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;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 United States, or &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:SignificantAccountingPoliciesTextBlock
      contextRef="c20240101to20240630"
      id="Text_3f631d62f8b3441ca8993f923978bb09">
&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;"&gt;Our significant accounting policies have not changed substantially from those included in our Annual Report on Form 10-K for the year
    ended December 31, 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Recently Issued 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;We do not expect any recently issued accounting standards to have a material impact to our financial results.&lt;/div&gt;
</us-gaap:SignificantAccountingPoliciesTextBlock>
    <us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock
      contextRef="c20240101to20240630"
      id="Text_77f04263f8fd40e2bb811ff95d88cebe">
&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;Recently Issued 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;We do not expect any recently issued accounting standards to have a material impact to our financial results.&lt;/div&gt;
</us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock>
    <us-gaap:SupplementalBalanceSheetDisclosuresTextBlock
      contextRef="c20240101to20240630"
      id="Text_9c86d5826cfc4e50b92f86949d3b9fca">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;3. Supplemental Financial Data&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;Inventories&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; white-space: nowrap;" valign="bottom"&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; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;June 30, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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, 2023&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; 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;Raw materials:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; 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; 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; white-space: nowrap;" 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; 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;22,211&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;20,985&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; white-space: nowrap;" 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; 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; 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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,412&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; 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; 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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,809&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; white-space: nowrap;" 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; 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;24,623&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;22,794&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%; white-space: nowrap;" 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%; 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;3,614&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;5,477&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; white-space: nowrap;" 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; 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;486&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;154&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; white-space: nowrap;" 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 inventories&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;28,723&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;28,425&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="text-align: left; 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; white-space: nowrap;" valign="bottom"&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; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;June 30, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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, 2023&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; white-space: nowrap;" 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; 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;82,017&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;105,967&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%; white-space: nowrap;" 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%; 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;10,603&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;7,454&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: 76%; background-color: #CCEEFF; white-space: nowrap;" 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; 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;4,583&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;4,875&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; white-space: nowrap;" 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; 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; 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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,127&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; 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; 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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;29,598&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" 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; 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; 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%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;114,330&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; 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; 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%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;147,894&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;
</us-gaap:SupplementalBalanceSheetDisclosuresTextBlock>
    <us-gaap:ScheduleOfInventoryCurrentTableTextBlock
      contextRef="c20240101to20240630"
      id="Text_8ca956cffe974ce9a840a246a97aa16c">
&lt;div style="display:none;"&gt;&lt;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;Inventories&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; white-space: nowrap;" valign="bottom"&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; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;June 30, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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, 2023&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; 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;Raw materials:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; 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; 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; white-space: nowrap;" 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; 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;22,211&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;20,985&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; white-space: nowrap;" 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; 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; 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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,412&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; 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; 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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,809&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; white-space: nowrap;" 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; 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;24,623&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;22,794&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%; white-space: nowrap;" 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%; 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;3,614&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;5,477&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; white-space: nowrap;" 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; 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;486&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;154&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; white-space: nowrap;" 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 inventories&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;28,723&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;28,425&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:ScheduleOfInventoryCurrentTableTextBlock>
    <us-gaap:InventoryRawMaterials
      contextRef="c20240630_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
      id="Fact_3043726b7f0d40479abbe8c68900b93f"
      unitRef="U002">22211000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20231231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
      id="Fact_6cec13c5f4334a1ba6216a6bc406747c"
      unitRef="U002">20985000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20240630_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
      decimals="-3"
      id="Fact_4a8280762bb1470eace824e402d6b623"
      unitRef="U002">2412000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20231231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
      decimals="-3"
      id="Fact_cf1accaf2b004921b424e5cd65e40c1f"
      unitRef="U002">1809000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20240630"
      decimals="-3"
      id="Fact_9975fb0b2fa74f9e8ab81ebad8fb2237"
      unitRef="U002">24623000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20231231"
      decimals="-3"
      id="Fact_e3f1efde1cdb414796dec720e17eac54"
      unitRef="U002">22794000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20240630"
      decimals="-3"
      id="Fact_e7c4b729eb5c4047a12ddaf1f657b647"
      unitRef="U002">3614000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20231231"
      decimals="-3"
      id="Fact_182d548d120f4e1daae74044c3e1bbe5"
      unitRef="U002">5477000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20240630"
      decimals="-3"
      id="Fact_b21c128f10e14f89b4963ecd92676ea1"
      unitRef="U002">486000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20231231"
      decimals="-3"
      id="Fact_70a3a016ecb849cd9021230823cf224d"
      unitRef="U002">154000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryNet
      contextRef="c20240630"
      decimals="-3"
      id="Fact_6f6a7ebaae1b4d95ace7fcfcf1fba210"
      unitRef="U002">28723000</us-gaap:InventoryNet>
    <us-gaap:InventoryNet
      contextRef="c20231231"
      decimals="-3"
      id="Fact_3e4c02edf53745679ae7e698216e7837"
      unitRef="U002">28425000</us-gaap:InventoryNet>
    <us-gaap:ScheduleOfAccruedLiabilitiesTableTextBlock
      contextRef="c20240101to20240630"
      id="Text_2a5416376d8f443abf966ca8534832b3">
&lt;div style="text-align: left; 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; white-space: nowrap;" valign="bottom"&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; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;June 30, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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, 2023&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; white-space: nowrap;" 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; 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;82,017&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;105,967&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%; white-space: nowrap;" 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%; 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;10,603&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;7,454&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: 76%; background-color: #CCEEFF; white-space: nowrap;" 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; 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;4,583&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;4,875&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; white-space: nowrap;" 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; 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; 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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,127&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; 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; 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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;29,598&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" 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; 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; 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%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;114,330&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; 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; 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%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;147,894&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;
</us-gaap:ScheduleOfAccruedLiabilitiesTableTextBlock>
    <ions:AccruedClinicalDevelopmentExpenses
      contextRef="c20240630"
      decimals="-3"
      id="Fact_9fa65e9eb4874e529d2b5a8558dbeefc"
      unitRef="U002">82017000</ions:AccruedClinicalDevelopmentExpenses>
    <ions:AccruedClinicalDevelopmentExpenses
      contextRef="c20231231"
      decimals="-3"
      id="Fact_e1554d35bd0e4c82aabac0d765ba6ddc"
      unitRef="U002">105967000</ions:AccruedClinicalDevelopmentExpenses>
    <ions:AccruedInLicensingFeesCurrent
      contextRef="c20240630"
      decimals="-3"
      id="Fact_c222f622055145968e8cd08ff3a569bd"
      unitRef="U002">10603000</ions:AccruedInLicensingFeesCurrent>
    <ions:AccruedInLicensingFeesCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_7076c86dd1604e5a826b9716b8c0ca6e"
      unitRef="U002">7454000</ions:AccruedInLicensingFeesCurrent>
    <ions:AccruedCommercialExpensesCurrent
      contextRef="c20240630"
      decimals="-3"
      id="Fact_74d1a19cf230440593ea60ac85e2acd3"
      unitRef="U002">4583000</ions:AccruedCommercialExpensesCurrent>
    <ions:AccruedCommercialExpensesCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_0c409149156e4e1bb3090f026e0406df"
      unitRef="U002">4875000</ions:AccruedCommercialExpensesCurrent>
    <us-gaap:OtherAccruedLiabilitiesCurrent
      contextRef="c20240630"
      decimals="-3"
      id="Fact_9ed0b35c739e48bbb51027c4ea2073ae"
      unitRef="U002">17127000</us-gaap:OtherAccruedLiabilitiesCurrent>
    <us-gaap:OtherAccruedLiabilitiesCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_b95beacb8e88464e9674b3d0a46cdaf4"
      unitRef="U002">29598000</us-gaap:OtherAccruedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20240630"
      decimals="-3"
      id="Fact_eda2e67f42534d11b5f9b63e05969ad1"
      unitRef="U002">114330000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_e41fd559b7f64fab9ce5f7f42569b6db"
      unitRef="U002">147894000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:RevenueFromContractWithCustomerTextBlock
      contextRef="c20240101to20240630"
      id="Text_1284d7033f3441c5834281acfd6f5060">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;4. Revenues&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 six months ended June 30, 2024 and 2023, our revenues were
    comprised 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;/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;June 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;Six 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;June 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;2024&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;2023&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;2024&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;2023&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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&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;" 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;Commercial revenue:&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: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&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;56,743&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;61,012&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;95,198&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;111,258&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: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;WAINUA royalties&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;3,781&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;4,907&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: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other 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;&#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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;TEGSEDI and WAYLIVRA revenue, net&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;8,192&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;10,655&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;16,820&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;17,133&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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Licensing and other royalty revenue&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;3,320&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;6,230&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;14,704&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;17,273&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; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total other commercial 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;11,512&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;16,885&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;31,524&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;34,406&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: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total 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;&#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;72,036&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;77,897&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;&#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;131,629&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;145,664&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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research and development 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;&#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; 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;&#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; 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;&#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; 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;&#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;/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; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Collaborative agreement 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;&#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;141,524&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;91,013&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;190,870&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;&#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;129,347&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; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;WAINUA joint development 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;11,690&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;19,501&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;22,249&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;43,924&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: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total research and development revenue&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;153,214&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;110,514&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;213,119&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;173,271&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: 54pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue&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;225,250&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;188,411&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;344,748&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;318,935&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; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;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;The following are sources of revenue and when we typically recognize 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: SPINRAZA royalties and WAINUA 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;We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. In 2024, we began earning royalties from
    WAINUA 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; 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;We earn commercial revenue from TEGSEDI and WAYLIVRA sales under our distribution agreements with Sobi. In addition, we receive royalties
    from PTC Therapeutics International Limited, or PTC, for TEGSEDI&#160; and WAYLIVRA 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; font-style: italic;"&gt;Commercial Revenue: 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;&#160;We also recognize as commercial revenue sales milestone payments and royalties we earn under our partnerships. For example, we earn
    royalty revenue on net sales of QALSODY, which is included in 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; font-style: italic;"&gt;Research and development revenue under collaboration 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Upfront payments:&lt;/span&gt;&lt;/span&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. If part or all of the upfront payment is a license fee, we recognize as revenue the portion related to the license when we deliver the license to our partner because our partner has full use of
    the license and we do not have any additional performance obligations related to the license after delivery.&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; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Milestone payments:&lt;/span&gt;&lt;/span&gt; We
    include variable 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 R&amp;amp;D 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, when we
    achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&amp;amp;D services performance obligation and
    recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone payment to 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;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.&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; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;License fees:&lt;/span&gt;&lt;/span&gt; We 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 because our partner has full use of the license and we do not have any additional performance obligations
    related to the license after delivery.&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;WAINUA (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 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize WAINUA for the
    treatment of transthyretin amyloidosis, or ATTR. We jointly developed and are commercializing WAINUA&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;with AstraZeneca in the U.S. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for the treatment of adults with polyneuropathy caused by hereditary ATTR, or ATTRv-PN.&lt;/span&gt; We initially granted AstraZeneca exclusive rights to commercialize WAINUA outside the U.S., except for
    certain Latin American countries. In 2023, we expanded those rights to include 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 WAINUA 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 Accounting Standards Codification, or ASC, Topic 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;, or ASC 606, for the license we granted to AstraZeneca and as a result we had one performance obligation. 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 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, 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 currently 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 WAINUA 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 selling,
    general and administrative, or SG&amp;amp;A, expense and R&amp;amp;D expense, respectively.&lt;/div&gt;
</us-gaap:RevenueFromContractWithCustomerTextBlock>
    <us-gaap:DisaggregationOfRevenueTableTextBlock
      contextRef="c20240101to20240630"
      id="Text_f2e15c2700584bae9782b0e80d3a26fc">
&lt;div style="display:none;"&gt;&lt;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 six months ended June 30, 2024 and 2023, our revenues were
    comprised 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;/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;June 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;Six 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;June 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;2024&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;2023&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;2024&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;2023&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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&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;" 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;Commercial revenue:&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: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&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;56,743&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;61,012&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;95,198&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;111,258&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: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;WAINUA royalties&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;3,781&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;4,907&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: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other 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;&#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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;TEGSEDI and WAYLIVRA revenue, net&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;8,192&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;10,655&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;16,820&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;17,133&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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Licensing and other royalty revenue&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;3,320&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;6,230&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;14,704&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;17,273&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; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total other commercial 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;11,512&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;16,885&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;31,524&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;34,406&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: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total 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;&#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;72,036&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;77,897&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;&#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;131,629&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;145,664&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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research and development 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;&#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; 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;&#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; 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;&#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; 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;&#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;/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; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Collaborative agreement 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;&#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;141,524&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;91,013&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;190,870&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;&#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;129,347&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; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;WAINUA joint development 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;11,690&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;19,501&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;22,249&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;43,924&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: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total research and development revenue&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;153,214&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;110,514&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;213,119&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;173,271&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: 54pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue&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;225,250&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;188,411&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;344,748&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;318,935&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;


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    <ions:UpfrontPaymentReceived
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;5.&#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 AstraZeneca, Biogen, Otsuka and
      Roche collaborations, which are the collaborations with substantive changes during 2024 from those included in Part IV, Item 15, Note 4, &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;, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2023.&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;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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; collaborations with AstraZeneca, &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; focused on the joint development and commercialization of WAINUA and &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; focused on the treatment of cardiovascular, renal and metabolic diseases. From inception through &lt;/span&gt;June 30, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we have received more than $&lt;/span&gt;920&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million from these collaborations.&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;Over the term of our WAINUA collaboration, we are eligible to receive up to $3.6 billion, which is comprised of a $200 million upfront payment, up to $485 million in development and approval milestone payments and up to $2.9 billion in sales milestone payments. The agreement includes territory-specific development, commercial and medical affairs cost-sharing provisions. In addition, we are eligible to receive up
    to mid-20 percent royalties for sales in the U.S. and tiered royalties up to the high teens for sales outside the U.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;In January 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with ATTRv-PN. As a result, we began earning
    royalties from WAINUA sales, which we recognize as commercial revenue in our condensed consolidated statements of operations. We will achieve the next payment of up to $30 million upon regulatory approval of WAINUA for ATTRv-PN in the European Union, or EU, under this 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;"&gt;During the three and six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with AstraZeneca (in thousands, 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;/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;June 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;Six 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;June 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;2024&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;2023&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;2024&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;2023&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;Revenue from our relationship with AstraZeneca&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;15,960&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;59,501&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;27,645&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;83,926&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;7&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;32&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;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;
          &lt;div style="font-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;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;/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 June 30, 2024 included deferred contract revenue of $1.9 million from our relationship
    with AstraZeneca. We did not have any deferred contract revenue from our relationship with AstraZeneca at December 31, 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; 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. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. QALSODY, our medicine to treat patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS,
    received accelerated approval from the U.S. Food and Drug Administration, or FDA, in April 2023 and marketing authorization under exceptional circumstances from the European Medicines Agency, or EMA, in May 2024. In addition, we and Biogen are
    currently developing numerous other investigational medicines to treat neurodegenerative diseases, including medicines in development to treat people with amyotrophic lateral sclerosis, or ALS, SMA, Alzheimer&#x2019;s disease, or AD, and Parkinson&#x2019;s disease,
    or PD. 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 June 30, 2024, we have received more than $3.9 billion in payments from our Biogen
    collaborations, including payments to purchase our stock.&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 2013 strategic neurology collaboration, we earned a $20 million milestone payment from Biogen when the EMA approved Biogen&#x2019;s Marketing Authorization Application, or MAA, filing of QALSODY in the second quarter of 2024. We recognized this milestone
    payment as R&amp;amp;D revenue in full in the second quarter of 2024 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next milestone payment for QALSODY of $10 million if the Ministry of Health, Labour and Welfare of Japan approves Biogen&#x2019;s Japanese New Drug Application filing of QALSODY.&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 second quarter of 2024, Biogen's option to license ION582, an investigational antisense medicine for the potential treatment of
    Angelman Syndrome, expired unexercised. As a result, we recognized $30 million of R&amp;amp;D revenue from previously deferred milestone payments
    related to the ION582 study because we did not have any remaining performance obligations. We will achieve the next milestone payment of $25
    million if Biogen advances IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; into Phase 3 development under our 2012 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;"&gt;During the three and six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Biogen (in thousands, 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;/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;June 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;Six 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;June 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;2024&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;2023&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;2024&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;2023&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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Biogen&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;138,159&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;97,402&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;197,395&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;167,903&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: -8.9pt; 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;61&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;52&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;57&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;53&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 sheets at June 30, 2024 and December 31, 2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;included deferred contract revenue of $241.8 million and $307.4 million, respectively, from 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; font-style: italic; font-weight: bold;"&gt;Otsuka&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 2023, we entered into an agreement with Otsuka
      Pharmaceutical Co., Ltd., or Otsuka, to commercialize donidalorsen in Europe. In the second quarter of 2024, we expanded the agreement to include commercialization rights for donidalorsen in the Asia-Pacific region in addition to Europe. As a result,
      we received a $&lt;/span&gt;20&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment from Otsuka.
      Under the amended agreement, we are eligible to receive up to $&lt;/span&gt;290&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, which is comprised of $&lt;/span&gt;85&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in
      upfront payments, up to $&lt;/span&gt;65&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in regulatory milestone
      payments and up to $&lt;/span&gt;140&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in sales milestone payments
      over the term of the collaboration. In addition, we are eligible to receive tiered royalties up to &lt;/span&gt;30 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; on net sales. We are responsible for completing the ongoing development of donidalorsen. We retained the rights to commercialize donidalorsen in the U.S. and in the rest of the world, assuming
      regulatory approvals. &lt;/span&gt;From inception through June 30, 2024, we have received $85 million in payments from Otsuka.&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 identified two performance
    obligations under our amended agreement for the Asia-Pacific region, comprised of our license of donidalorsen to Otsuka and R&amp;amp;D services for donidalorsen. We allocated the transaction price of $20 million based on the estimated stand-alone selling price of each performance obligation 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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;$17.5 million for the license of donidalorsen; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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;$2.5 million for the R&amp;amp;D services for donidalorsen.&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;In the second quarter of 2024, we recognized $17.5
    million as revenue in full because Otsuka had full use of the license without any continuing involvement from us. We are recognizing revenue for our R&amp;amp;D services performance obligation as we perform services based on our effort to satisfy our
    performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our R&amp;amp;D services performance obligation in March 2026. We will achieve the next payment of $15 million if the EMA accepts a MAA filing for donidalorsen in the EU under this 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;"&gt;During the three and six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Otsuka (in thousands, 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;/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;June 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;Six 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;June 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;2024&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;2023&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;2024&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;2023&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;Revenue from our relationship with Otsuka&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;18,905&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;19,691&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;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;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;
          &lt;div style="font-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&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;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;
          &lt;div style="font-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&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 sheets at June 30, 2024 and December 31, 2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;included deferred contract revenue of $8.8 million and $8.5 million, respectively, from our relationship with Otsuka.&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 three collaborations
    with Hoffmann-La Roche Inc. and F. Hoffmann-La Roche Ltd, collectively Roche: 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&#x2019;s disease, or HD, 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 immunoglobulin A, or IgA, nephropathy, or IgAN, and one to develop RNA-targeted programs for AD and HD. From inception through June 30, 2024, we have received more than $345 million in payments 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In July 2024, Roche discontinued development&lt;/span&gt; of
    IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt; for the treatment of geographic atrophy, or GA, following the completion of the Phase 2 study, which showed a favorable safety profile and target engagement, but insufficient efficacy to advance into Phase 3 development.&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;Over the term of the IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt; collaboration for the treatment of IgAN, we are eligible to receive up to $430 million, which is comprised of a $35 million
    license fee, up to $25 million in development milestone payments, up to $90 million in regulatory milestone payments and up to $280 million in sales milestone
    payments. We will achieve the next payment of $23.5 million if Roche advances IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt; for the treatment of IgAN under this
    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;"&gt;During the three and six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Roche (in thousands, 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;June 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;Six 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;June 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;2024&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;2023&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;2024&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;2023&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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Roche&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;11,089&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;5,754&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;22,595&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;8,121&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;5&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;7&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 sheets at June 30, 2024 and December 31, 2023 included deferred contract revenue of $15.0 million and $36.7 million, respectively,
    from our relationship with Roche.&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 six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with AstraZeneca (in thousands, 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;/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;June 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;Six 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;June 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;2024&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;2023&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;2024&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;2023&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;Revenue from our relationship with AstraZeneca&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;15,960&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;59,501&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;27,645&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;83,926&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;7&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;32&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;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;
          &lt;div style="font-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;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;/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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three and six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Biogen (in thousands, 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;/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;June 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;Six 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;June 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;2024&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;2023&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;2024&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;2023&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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Biogen&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;138,159&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;97,402&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;197,395&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;167,903&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: -8.9pt; 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;61&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;52&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;57&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;53&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;


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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 six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Otsuka (in thousands, 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;/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;June 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;Six 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;June 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;2024&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;2023&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;2024&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;2023&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;Revenue from our relationship with Otsuka&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;18,905&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;19,691&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;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;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;
          &lt;div style="font-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;
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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;div style="display:none;"&gt;&lt;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 six months ended June 30, 2024 and 2023, we earned the following revenue from our relationship with Roche (in thousands, 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;June 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;Six 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;June 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;2024&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;2023&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;2024&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;2023&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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Roche&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;11,089&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;5,754&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;22,595&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;8,121&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;5&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;7&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;


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      contextRef="c20230401to20230630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember"
      decimals="2"
      id="Fact_9cf6fe977f204899bcd61b2efcb1db6b"
      unitRef="U003">0.03</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20240101to20240630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember"
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      unitRef="U003">0.07</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20230101to20230630_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember"
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      contextRef="c20240630_TypeOfArrangementAxis_RocheCollaborationsMember"
      decimals="-5"
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      unitRef="U002">15000000</us-gaap:ContractWithCustomerLiability>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationsMember"
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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. 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-weight: bold;"&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 six months ended&#160;June 30, 2024 and 2023 by dividing our net loss by our weighted-average number of common shares outstanding during the 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;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 six months ended&#160;June 30, 2024 and 2023, 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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;1.75 percent convertible senior notes, or 1.75% 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additionally, as of June 30, 2024
    and 2023, 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;
</us-gaap:EarningsPerShareTextBlock>
    <us-gaap:EarningsPerSharePolicyTextBlock
      contextRef="c20240101to20240630"
      id="Text_9471c38bb7ae4e1287d0671ecea462a6">
&lt;div style="display:none;"&gt;&lt;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;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 six months ended&#160;June 30, 2024 and 2023 by dividing our net loss by our weighted-average number of common shares outstanding during the 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;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 six months ended&#160;June 30, 2024 and 2023, 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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;1.75 percent convertible senior notes, or 1.75% 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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&gt;

    &lt;td style="width: 18pt; vertical-align: top; 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additionally, as of June 30, 2024
    and 2023, 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;
</us-gaap:EarningsPerSharePolicyTextBlock>
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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;7.&#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 June 30, 2024:&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: 9pt; 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;75&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: 9pt; 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;21&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: 9pt; 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;4&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: 9pt; 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 June 30, 2024,
    96 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.&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 debt 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, 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 June 30, 2024, we had an
    equity ownership interest of less than 20 percent in seven 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: justify; 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&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;/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; 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; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;June 30, 2024&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 debt 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;552,837&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;36&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;(1,569&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;551,304&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;121,781&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&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;(310&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;121,476&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;650,997&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&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;(1,105&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;649,904&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;18,083&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;14&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;(42&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;18,055&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 debt 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;1,343,698&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;67&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;(3,026&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;1,340,739&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;218,639&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;191&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;(874&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;217,956&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;115,349&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;72&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;(317&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;115,104&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;127,240&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;(1,135&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;126,117&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;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; 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;1,668&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;(8&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;1,660&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 debt 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;" 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;462,896&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;275&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;(2,334&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;460,837&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;&#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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale 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;
          &lt;div style="font-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;1,806,594&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;342&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;(5,360&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;
          &lt;div style="font-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;1,801,576&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;&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%;" 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;&#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; 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;&#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; 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;&#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; 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;&#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;/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;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%; 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;11,897&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;&#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;334&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;(5,377&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;6,854&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;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;" 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;23,115&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;25,001&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;(7,093&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;41,023&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 equity 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;35,012&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;25,335&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;(12,470&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;47,877&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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale debt and equity securities&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;1,841,606&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;25,677&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;(17,830&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;" 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;1,849,453&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;/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; 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; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;December 31, 2023&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 debt 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;559,967&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;157&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;(2,625&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;557,499&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;224,711&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;64&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;(611&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;224,164&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;513,784&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;152&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;(1,889&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;512,047&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;17,757&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;42&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;(113&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;17,686&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 debt 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;1,316,219&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;415&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;(5,238&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;1,311,396&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;243,151&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;1,270&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;(692&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;243,729&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;110,138&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;547&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;(21&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;110,664&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;294,873&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;1,239&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;(480&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;295,632&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;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; 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;3,466&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&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;(4&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;3,469&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 debt 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;" 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;651,628&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;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;3,063&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;(1,197&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;653,494&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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale 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;
          &lt;div style="font-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;1,967,847&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;3,478&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;(6,435&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;
          &lt;div style="font-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;1,964,890&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;&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%;" 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;&#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; 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;&#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; 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;&#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; 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;&#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;/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;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%; 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;11,897&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;&#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;236&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;(5,832&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;6,301&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;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;" 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;23,115&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;25,001&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;(5,125&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;42,991&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 equity 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;35,012&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;25,237&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;(10,957&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;49,292&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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale debt and equity securities&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;2,002,859&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;28,715&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;(17,392&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;" 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;2,014,182&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="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; 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 sheets.&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; 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 publicly traded equity securities are
            included in other current assets. We recognize publicly traded equity securities at fair value. In the six months ended&#160;June 30, 2024, we recorded a $0.6
            million net unrealized gain in our condensed consolidated statements of operations related to changes 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; 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 privately held equity securities are included in deposits and other assets. We recognize our privately held 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, which are Level 3 inputs&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. In the &lt;/span&gt;six months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;June 30, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we recorded a loss of $&lt;/span&gt;2.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in our condensed consolidated statements of operations related to changes in the
              fair value of our investments in privately held companies.&lt;/span&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;The following is a summary of our investments we consider to be temporarily impaired at June 30, 2024 (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;" valign="bottom"&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;&#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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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;440&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;517,394&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;(1,155&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;142,390&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;(1,288&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;659,784&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;(2,443&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%;" 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;108&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;173,618&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;(482&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;25,892&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;(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;
          &lt;div style="font-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;199,510&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;(627&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;" 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;71&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;561,363&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;(862&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;154,006&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;(1,378&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;715,369&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;(2,240&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%; 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;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;8,449&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&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;9,319&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;(27&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;17,768&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;(50&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; 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 temporarily impaired 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;&#160;&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;664&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;1,260,824&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;(2,522&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;331,607&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;(2,838&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;1,592,431&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;(5,360&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;/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;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 intend to hold these securities
    to maturity and anticipate full recovery of our debt securities&#x2019; amortized cost basis at maturity.&lt;/div&gt;
</us-gaap:InvestmentTextBlock>
    <us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock
      contextRef="c20240101to20240630"
      id="Text_0fd547c923744c79bd4f06c68a515bf2">
&lt;div style="display:none;"&gt;&lt;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 June 30, 2024:&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: 9pt; 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;75&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: 9pt; 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;21&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: 9pt; 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;4&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: 9pt; 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;
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    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage
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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 (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;/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; 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; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;June 30, 2024&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 debt 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;552,837&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;36&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;(1,569&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;551,304&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;121,781&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&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;(310&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;121,476&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;650,997&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&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;(1,105&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;649,904&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;18,083&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;14&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;(42&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;18,055&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 debt 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;1,343,698&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;67&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;(3,026&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;1,340,739&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;218,639&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;191&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;(874&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;217,956&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;115,349&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;72&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;(317&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;115,104&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;127,240&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;(1,135&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;126,117&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;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; 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;1,668&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;(8&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;1,660&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 debt 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;" 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;462,896&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;275&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;(2,334&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;460,837&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;&#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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale 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;
          &lt;div style="font-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;1,806,594&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;342&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;(5,360&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;
          &lt;div style="font-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;1,801,576&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;&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%;" 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;&#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; 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;&#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; 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;&#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; 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;&#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;/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;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%; 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;11,897&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;&#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;334&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;(5,377&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;6,854&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;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;" 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;23,115&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;25,001&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;(7,093&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;41,023&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 equity 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;35,012&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;25,335&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;(12,470&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;47,877&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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale debt and equity securities&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;1,841,606&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;25,677&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;(17,830&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;" 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;1,849,453&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;/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; 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; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;December 31, 2023&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 debt 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;559,967&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;157&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;(2,625&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;557,499&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;224,711&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;64&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;(611&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;224,164&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;513,784&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;152&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;(1,889&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;512,047&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;17,757&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;42&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;(113&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;17,686&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 debt 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;1,316,219&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;415&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;(5,238&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;1,311,396&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;243,151&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;1,270&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;(692&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;243,729&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;110,138&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;547&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;(21&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;110,664&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;294,873&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;1,239&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;(480&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;295,632&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;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; 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;3,466&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&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;(4&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;3,469&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 debt 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;" 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;651,628&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;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;3,063&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;(1,197&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;653,494&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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale 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;
          &lt;div style="font-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;1,967,847&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;3,478&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;(6,435&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;
          &lt;div style="font-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;1,964,890&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;&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%;" 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;&#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; 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;&#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; 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;&#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; 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;&#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;/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;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%; 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;11,897&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;&#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;236&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;(5,832&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;6,301&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;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;" 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;23,115&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;25,001&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;(5,125&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;42,991&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 equity 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;35,012&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;25,237&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;(10,957&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;49,292&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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale debt and equity securities&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;2,002,859&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;28,715&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;(17,392&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;" 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;2,014,182&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="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; 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 sheets.&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; 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 publicly traded equity securities are
            included in other current assets. We recognize publicly traded equity securities at fair value. In the six months ended&#160;June 30, 2024, we recorded a $0.6
            million net unrealized gain in our condensed consolidated statements of operations related to changes 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; 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 privately held equity securities are included in deposits and other assets. We recognize our privately held 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, which are Level 3 inputs&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. In the &lt;/span&gt;six months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;June 30, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we recorded a loss of $&lt;/span&gt;2.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in our condensed consolidated statements of operations related to changes in the
              fair value of our investments in privately held companies.&lt;/span&gt;&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: 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 June 30, 2024 (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;" valign="bottom"&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;&#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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;" 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;440&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;517,394&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;(1,155&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;142,390&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;(1,288&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;659,784&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;(2,443&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%;" 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;108&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;173,618&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;(482&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;25,892&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;(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;
          &lt;div style="font-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;199,510&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;(627&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;" 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;71&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;561,363&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;(862&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;154,006&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;(1,378&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;715,369&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;(2,240&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%; 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;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;8,449&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&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;9,319&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;(27&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;17,768&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;(50&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; 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 temporarily impaired 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;&#160;&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;664&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;
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    &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;1,260,824&lt;/div&gt;
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    &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;(2,522&lt;/div&gt;
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    &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;
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    &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;331,607&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;(2,838&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;1,592,431&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;(5,360&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;

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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.&#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;The following tables present the major security types we held at June 30, 2024 and December 31, 2023 that we regularly measure and carry at fair
    value. 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 security&#x2019;s 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;/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; white-space: nowrap;" 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;June 30, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; 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;212,489&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;212,489&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: 64%;" 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;769,260&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;769,260&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: 64%; 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;236,580&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;236,580&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: 64%;" 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;776,021&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;776,021&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: 64%; 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 (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;19,715&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;19,715&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: 64%; padding-bottom: 2px;" 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 (4)&lt;/div&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;6,854&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;6,854&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" 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; 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;2,020,919&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;995,364&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;1,025,555&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;/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; white-space: nowrap;" 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, 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; 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;185,424&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;
          &lt;div style="font-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;185,424&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;
          &lt;div style="font-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: 64%;" 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 (5)&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;801,228&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;801,228&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: 64%; 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;334,828&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;334,828&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: 64%;" 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;807,679&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;&#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;807,679&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;&#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: 64%; 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 (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;21,155&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;21,155&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: 64%; padding-bottom: 2px;" 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 (4)&lt;/div&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;6,301&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;6,301&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" 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; 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;2,156,615&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;999,404&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;1,157,211&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="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following footnotes reference lines in our condensed consolidated balance sheets:&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; 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.&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; 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;$16.9 million was included in cash and cash equivalents, with the difference 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; 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; 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;Included in other current assets.&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; 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;$33.0 million was included in cash and cash equivalents, with the difference 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;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;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 1.75% Notes, 0% Notes and 0.125% Notes had a fair
    value of $634.4 million, $649.6
    million and $43.4 million at June 30, 2024,
    respectively. Our 1.75% Notes, 0%
    Notes and 0.125% Notes had a fair value of $661.1
    million, $667.8 million and $42.4
    million at December 31, 2023, 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="c20240101to20240630"
      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 June 30, 2024 and December 31, 2023 that we regularly measure and carry at fair
    value. 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 security&#x2019;s 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;/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; white-space: nowrap;" 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;June 30, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; 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;212,489&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;212,489&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: 64%;" 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;769,260&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;769,260&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: 64%; 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;236,580&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;236,580&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: 64%;" 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;776,021&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;776,021&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: 64%; 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 (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;19,715&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;19,715&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: 64%; padding-bottom: 2px;" 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 (4)&lt;/div&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;6,854&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;6,854&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" 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; 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;2,020,919&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;995,364&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;1,025,555&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;/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; white-space: nowrap;" 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, 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; 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; white-space: nowrap;" 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;" 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; white-space: nowrap;" 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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; 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;185,424&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;
          &lt;div style="font-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;185,424&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;
          &lt;div style="font-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: 64%;" 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 (5)&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;801,228&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;801,228&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: 64%; 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;334,828&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;334,828&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: 64%;" 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;807,679&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;&#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;807,679&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;&#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: 64%; 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 (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;21,155&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;21,155&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: 64%; padding-bottom: 2px;" 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 (4)&lt;/div&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;6,301&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;6,301&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" 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; 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;2,156,615&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;999,404&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;1,157,211&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="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following footnotes reference lines in our condensed consolidated balance sheets:&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; 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.&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; 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;$16.9 million was included in cash and cash equivalents, with the difference 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; 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; 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;Included in other current assets.&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;

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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$33.0 million was included in cash and cash equivalents, with the difference included in short-term investments.&lt;/div&gt;
        &lt;/td&gt;

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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;9. 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;The following table summarizes stock-based compensation expense for the three and six months ended&#160;June 30, 2024 and 2023 (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&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;June 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;Six 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;June 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;/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;2024&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;2023&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;2024&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;2023&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;246&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;118&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;450&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;237&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;22,766&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;19,249&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;44,991&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;38,816&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;7,716&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;7,194&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;16,627&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;14,457&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;30,728&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;26,561&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;62,068&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;53,510&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 June 30, 2024, total
    unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $61.6 million, $96.7 million and $13.8 million, respectively. Our
    actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures, including any PRSUs that do not vest. 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 1.3 years, 1.6 years and 1.9 years, 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;Refer to Part IV, Item 15, 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, 2023 for further details on how we determine the fair value of stock options granted, RSUs, PRSUs and stock purchase rights under the 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;For the six months ended&#160;June 30, 2024 and 2023, 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;/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;Six 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;June 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;2024&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;2023&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;4.1&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;3.6&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;
          &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;43.9&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;47.3&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;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;/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;/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;Six 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;June 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;2024&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;2023&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;5.3&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;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;5.2&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;38.4&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;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;36.7&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;
          &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;RSUs:&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 weighted-average grant date fair value of RSUs granted to employees for the six months ended&#160;June 30, 2024 and 2023 was $52.60 and $39.50 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;PRSUs:&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 terms of the PRSUs we granted in 2024 and 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period
    based on our relative TSR as compared to a peer group of companies and as measured at the end of the 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
    to 200 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;The weighted-average grant date fair value of PRSUs we granted to our executive officers for the six months ended&#160;June 30, 2024 and 2023 was $78.41 and $58.99 per share, respectively.&lt;/div&gt;
</us-gaap:DisclosureOfCompensationRelatedCostsShareBasedPaymentsTextBlock>
    <us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock
      contextRef="c20240101to20240630"
      id="Text_41bb03e5346543ff85da32e114653473">
&lt;div style="display:none;"&gt;&lt;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 six months ended&#160;June 30, 2024 and 2023 (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&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;June 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;Six 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;June 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;/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;2024&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;2023&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;2024&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;2023&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;246&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;118&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;450&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;237&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;22,766&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;19,249&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;44,991&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;38,816&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;7,716&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;7,194&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;16,627&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;14,457&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;30,728&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;26,561&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;62,068&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;53,510&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;


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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;/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;Six 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;June 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;2024&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;2023&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;4.1&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;3.6&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;
          &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;43.9&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;47.3&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;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;

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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;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&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;Six 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;June 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;2024&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;2023&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;5.3&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;
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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;5.2&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;38.4&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;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;36.7&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;
          &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;


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    <us-gaap:IncomeTaxDisclosureTextBlock
      contextRef="c20240101to20240630"
      id="Text_d3ef5f132e9f4b459c8640b25e10b2da">
&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;10.&#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;We recorded income tax expense of $0.1
    million and $0.1 million for the three and six months ended&#160;June 30, 2024, respectively, compared to $7.8 million and $19.2 million for the same periods in 2023, respectively. The decrease in income tax expense relates primarily to the impact of the royalty purchase agreement with Royalty Pharma on income tax
    expense for the three and six months ended&#160;June 30, 2023. We reflected the Royalty Pharma transaction as a taxable sale, which required us to include the proceeds from the sale, net of currently deductible issuance costs, as taxable income in 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;We continue to maintain a full valuation allowance on all our net deferred tax assets.&lt;/div&gt;
</us-gaap:IncomeTaxDisclosureTextBlock>
    <us-gaap:IncomeTaxExpenseBenefit
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;11. Liability Related to Sale of Future 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;In January 2023, we entered into a royalty purchase agreement with Royalty Pharma to monetize a portion of our future SPINRAZA and
    pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. As a result, we received an upfront payment of $500
    million and we are eligible to receive up to $625 million in additional milestone payments. Under the terms of the agreement, Royalty Pharma will
    receive 25 percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to 45 percent of royalty payments in 2028, on up to $1.5 billion in annual sales. In
    addition, Royalty Pharma will receive 25 percent of any future royalty payments on pelacarsen, our medicine in development to treat patients
    with elevated lipoprotein(a)-driven cardiovascular disease. Royalty Pharma&#x2019;s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $475 million or $550 million, depending on the timing and occurrence of FDA approval of
    pelacarsen.&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 upfront payment of $500
    million as a liability related to the sale of future royalties, net of transaction costs of $10.4 million, which we are amortizing over the
    estimated life of the arrangement using the effective interest rate method. We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We record royalty payments made to Royalty
    Pharma as a reduction of the liability.&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 the effective interest rate used to record interest expense under this agreement based on an estimate of future royalty
    payments to Royalty Pharma. As of June 30, 2024, the estimated effective interest rate under the agreement was 13.5 percent.&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 sets forth information on our liability related to sale of future royalties
    (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: 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;Proceeds from sale of future royalties in January 2023&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;500,000&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;Issuance costs related to sale of future royalties&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;(10,434&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: 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;Royalty payments to Royalty Pharma&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;(44,628&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: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense related to sale of future royalties&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;68,238&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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amortization of issuance costs related to sale of future royalties&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;560&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: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net liability related to sale of future royalties as of December 31, 2023&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;513,736&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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Royalty payments to Royalty Pharma&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;(16,236&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: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense related to sale of future royalties&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;35,949&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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amortization of issuance costs related to sale of future royalties&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;305&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: top; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net liability related to sale of future royalties as of June 30, 2024&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;533,754&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;There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of royalty
    payments from Biogen and Novartis, and result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the commercial sales of SPINRAZA, the regulatory approval and commercial sales of
    pelacarsen, competing products or other significant events. &lt;/div&gt;
</us-gaap:OtherLiabilitiesDisclosureTextBlock>
    <ions:UpfrontRoyaltyPaymentReceived
      contextRef="c20230101to20230131_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-6"
      id="Fact_378c023c31584e55b0617bdf49309947"
      unitRef="U002">500000000</ions:UpfrontRoyaltyPaymentReceived>
    <ions:MaximumAmountOfPaymentsReceivableForAdditionalMilestones
      contextRef="c20240630_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-6"
      id="Fact_45c4a4d71b5f46aa8fc6a9fd8e84328e"
      unitRef="U002">625000000</ions:MaximumAmountOfPaymentsReceivableForAdditionalMilestones>
    <ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine
      contextRef="c20240630_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="2"
      id="Fact_01f145be530749a2b5f41c92469f3150"
      unitRef="U003">0.25</ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine>
    <ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine
      contextRef="c20240630_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="2"
      id="Fact_4defe32cd3804cbb97e4c7a2e3a297be"
      unitRef="U003">0.45</ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine>
    <ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid
      contextRef="c20240630_ProductOrServiceAxis_SpinrazaMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-8"
      id="Fact_4af0123d3f9a49d28566cdb7b703162e"
      unitRef="U002">1500000000</ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid>
    <ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine
      contextRef="c20240630_ProductOrServiceAxis_PelacarsenMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="2"
      id="Fact_5ab159c91cd6498eabdc7aec74f5b116"
      unitRef="U003">0.25</ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine>
    <ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack
      contextRef="c20240630_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-6"
      id="Fact_8efbfdbd4aec4c57ba48a38ed1338a40"
      unitRef="U002">475000000</ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack>
    <ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack
      contextRef="c20240630_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-6"
      id="Fact_d8115145c7914c85b8aa1e8af6fd697a"
      unitRef="U002">550000000</ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack>
    <ions:UpfrontRoyaltyPaymentReceived
      contextRef="c20230101to20230131_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-6"
      id="Fact_9289646b66ea4d879d32f2749df14834"
      unitRef="U002">500000000</ions:UpfrontRoyaltyPaymentReceived>
    <ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-5"
      id="Fact_0d96a5f873d84c6c9e556c6b4c988070"
      unitRef="U002">10400000</ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties>
    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
      contextRef="c20240630_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="3"
      id="Fact_b086ad26f3df4c96a5fb5a381fd3f7e6"
      unitRef="U003">0.135</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
    <us-gaap:OtherNoncurrentLiabilitiesTableTextBlock
      contextRef="c20240101to20240630"
      id="Text_96e6cdff125b48ec820d34ebadba6671">
&lt;div style="display:none;"&gt;&lt;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 sets forth information on our liability related to sale of future royalties
    (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: 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;Proceeds from sale of future royalties in January 2023&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;500,000&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;Issuance costs related to sale of future royalties&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;(10,434&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: 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;Royalty payments to Royalty Pharma&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;(44,628&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: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense related to sale of future royalties&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;68,238&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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amortization of issuance costs related to sale of future royalties&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;560&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: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net liability related to sale of future royalties as of December 31, 2023&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;513,736&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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Royalty payments to Royalty Pharma&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;(16,236&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: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense related to sale of future royalties&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;35,949&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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amortization of issuance costs related to sale of future royalties&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;305&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: top; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net liability related to sale of future royalties as of June 30, 2024&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;533,754&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:OtherNoncurrentLiabilitiesTableTextBlock>
    <ions:ProceedsFromSaleOfFutureRoyalties
      contextRef="c20230101to20230131_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_43ce69c69d2e4a9f981a2bd01cf03a45"
      unitRef="U002">500000000</ions:ProceedsFromSaleOfFutureRoyalties>
    <ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_72f284990c0f4d5eaa9acbc3d2493707"
      unitRef="U002">10434000</ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties>
    <ions:RoyaltyPayments
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_8ae2ba857c9b4817b07e3f9a9503ba12"
      unitRef="U002">44628000</ions:RoyaltyPayments>
    <ions:InterestExpenseRelatedToSaleOfFutureRoyalties
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_2a5f792f09cd4fbcbd0efc16a57bb504"
      unitRef="U002">68238000</ions:InterestExpenseRelatedToSaleOfFutureRoyalties>
    <ions:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_dbf1a3a7ce1b4932b155049240c94a4a"
      unitRef="U002">560000</ions:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties>
    <ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet
      contextRef="c20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_886a4872d05440beac01bb5287b39251"
      unitRef="U002">513736000</ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet>
    <ions:RoyaltyPayments
      contextRef="c20240101to20240630_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_507f8204b5a0488eaa3f8e7285488644"
      unitRef="U002">16236000</ions:RoyaltyPayments>
    <ions:InterestExpenseRelatedToSaleOfFutureRoyalties
      contextRef="c20240101to20240630_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_7f1f33033ed048b5b01a9e5613dea9ce"
      unitRef="U002">35949000</ions:InterestExpenseRelatedToSaleOfFutureRoyalties>
    <ions:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties
      contextRef="c20240101to20240630_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_04391b8b969944e9b5fb4ee32f9f9b92"
      unitRef="U002">305000</ions:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties>
    <ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet
      contextRef="c20240630_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_3b7b9d43c6f54a7cacb07fc1a05bb2bc"
      unitRef="U002">533754000</ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet>
    <us-gaap:DebtDisclosureTextBlock
      contextRef="c20240101to20240630"
      id="Text_932c025cb1a047c69adb81a74fc1d444">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;12. 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;1.75 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 2023, we completed a $575.0
    million offering of convertible senior notes and used $488.2 million of the net proceeds from the issuance of the 1.75% Notes to repurchase $504.4 million in
    principal of our 0.125% Notes. We expect to use the remaining net proceeds to settle the 0.125% Notes that remain outstanding and for general corporate and working capital purposes.&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 June 30, 2024, we had the following
    1.75% Notes outstanding (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;/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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1.75% 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;575.0&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;11.4&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_ac460e99cb6b43a8b64e987880ed0dd5"&gt;June 2028&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; width: 88%;" 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; 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;1.75&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: 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;Effective 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;2.3&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: 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;53.73&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;Total shares of common stock subject to conversion&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;10.7&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;/table&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: 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; font-style: italic;"&gt;0 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At June 30, 2024, we had the following &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes outstanding (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;/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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;0% 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;5.5&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_edbb9fb31e834f86ad026d22e567df04"&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; width: 88%;" 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; 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&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: 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;Effective 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;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: 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 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 &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes by increasing the effective conversion price on our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes. We increased our effective conversion price to $76.39
    with the same number of underlying shares as our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&#160;&lt;/span&gt;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 &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes, our note hedges are subject to adjustment. Additionally, our note hedges
    are exercisable upon conversion of the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes. The note
    hedges will expire upon maturity of the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes, or April
    2026. The note hedges and warrants are separate transactions and are not part of the terms of our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes. The holders of the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; 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 sheets. Refer to Part IV, Item 15, 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, 2023 for our Call Spread accounting policy. 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;As discussed above, in 2023, we repurchased $504.4
    million of our 0.125% 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;At June 30, 2024, we had the following
    0.125% Notes outstanding with interest payable semi-annually (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;/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; white-space: nowrap;" 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;44.5&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;0.1&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_9ad2e8b4fef74d3cab598aa38f5df4fd"&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; width: 88%;" 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; 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;0.125&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: 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;Effective 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;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: 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, excluding shares related to &lt;span style="text-indent: 0pt;"&gt;0.125&lt;/span&gt;% Notes that we have repurchased and are currently holding in 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;0.5&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 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. As of &lt;/span&gt;June 30, 2024&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, the note hedges and warrants remain outstanding.&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 sheets. 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;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;1.75%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, 0%
      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;&lt;/div&gt;
</us-gaap:DebtDisclosureTextBlock>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember"
      decimals="4"
      id="Fact_8fd7985775c44bfcace9d8ce7112cfeb"
      unitRef="U003">0.0175</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentFaceAmount
      contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember"
      decimals="-5"
      id="Fact_9ac73a0c76054664989ce3b276636b04"
      unitRef="U002">575000000</us-gaap:DebtInstrumentFaceAmount>
    <us-gaap:RepaymentsOfConvertibleDebt
      contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember"
      decimals="-5"
      id="Fact_e65b7027573d4d0fa002f8db903ff534"
      unitRef="U002">488200000</us-gaap:RepaymentsOfConvertibleDebt>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember"
      decimals="4"
      id="Fact_406d1a1bdf0b4ba1876e7c87768507dd"
      unitRef="U003">0.0175</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:RepaymentsOfConvertibleDebt
      contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-5"
      id="Fact_6adbda144ad541519a85f04742f7fe37"
      unitRef="U002">504400000</us-gaap:RepaymentsOfConvertibleDebt>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_aa260fe8f27f4107b319ed5903eeeac9"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20240630_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_c43b19935fcd4795b1b3242bab81b367"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:ConvertibleDebtTableTextBlock
      contextRef="c20240101to20240630_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember"
      id="Text_a6052bc8837240ebaade9f70205e7cda">
&lt;div style="display:none;"&gt;&lt;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 June 30, 2024, we had the following
    1.75% Notes outstanding (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;/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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1.75% 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;575.0&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;11.4&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_ac460e99cb6b43a8b64e987880ed0dd5"&gt;June 2028&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; width: 88%;" 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; 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;1.75&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: 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;Effective 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;2.3&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: 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;53.73&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;Total shares of common stock subject to conversion&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;10.7&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;/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: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At June 30, 2024, we had the following &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes outstanding (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;/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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;0% 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;5.5&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_edbb9fb31e834f86ad026d22e567df04"&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; width: 88%;" 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; 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&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: 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;Effective 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;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: 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;
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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 June 30, 2024, we had the following
    0.125% Notes outstanding with interest payable semi-annually (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;/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; white-space: nowrap;" 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;44.5&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;0.1&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_9ad2e8b4fef74d3cab598aa38f5df4fd"&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; width: 88%;" 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; 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;0.125&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: 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;Effective 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;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: 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, excluding shares related to &lt;span style="text-indent: 0pt;"&gt;0.125&lt;/span&gt;% Notes that we have repurchased and are currently holding in 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;0.5&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;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;13. 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;There are no pending material legal proceedings to which we are a party or of which our property is the subject.&lt;/div&gt;
</us-gaap:LegalMattersAndContingenciesTextBlock>
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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 quarter ended June 30, 2024, our Section 16 officers and directors adopted or terminated contracts, instructions or written plans for the purchase or sale of our securities as noted in the table below.&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; 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;Contract, instruction or written plan intended to satisfy the affirmative defense conditions of Rule 10b5-1(c) under the Exchange Act.&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: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;**&lt;/td&gt;

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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x201c;Non-Rule 10b5-1 trading arrangement&#x201d; as defined in item 408(c) of Regulation S-K under the Exchange Act.&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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;"&gt;


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        &lt;/td&gt;

    &lt;td rowspan="2" style="width: 2.22%; vertical-align: top;"&gt;&#160;&lt;/td&gt;

    &lt;td rowspan="2" style="width: 11.78%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;
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    &lt;td rowspan="2" style="width: 10.16%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Date&lt;/div&gt;
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    &lt;td rowspan="2" style="width: 2.22%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="3" style="width: 19.44%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;
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    &lt;td rowspan="2" style="width: 2.22%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td rowspan="2" style="width: 22.1%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;
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  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 7.98%; vertical-align: bottom; border-top: #000000 2px solid; border-bottom: #000000 2px solid;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Rule 10b5-1*&lt;/div&gt;
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    &lt;td style="width: 2.22%; vertical-align: top; border-top: #000000 2px solid;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 9.24%; vertical-align: bottom; border-top: #000000 2px solid; border-bottom: #000000 2px solid;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Non-Rule 10b5-1**&lt;/div&gt;
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  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 15.11%; vertical-align: top; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Brett P. Monia&lt;/div&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Chief Executive Officer&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 11.78%; vertical-align: top; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Termination&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 2.54%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 10.16%; vertical-align: top; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;June 26, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 7.98%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;X&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 9.24%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 10%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,442&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 2.22%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 22.1%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_916e87d3015b45708cd1e86a514e8307"&gt;Upon the execution of all instructions provided in the plan&lt;/span&gt;&lt;/div&gt;
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  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 15.11%; vertical-align: top; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Richard S. Geary&lt;/div&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;EVP, Chief Development Officer&lt;/div&gt;
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    &lt;td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 11.78%; vertical-align: top; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Adoption&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 2.54%; vertical-align: top; background-color: #FFFFFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 10.16%; vertical-align: top; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;April 8, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 7.98%; vertical-align: top; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;X&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 10%; vertical-align: top; background-color: #FFFFFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;241,732&lt;/div&gt;
        &lt;/td&gt;

    &lt;td style="width: 2.22%; vertical-align: top; background-color: #FFFFFF;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 22.1%; vertical-align: top; background-color: #FFFFFF;"&gt;
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        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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